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67 Cards in this Set

  • Front
  • Back

Peptide Group

- underlie all higher order structures


- a planar, rigid structure


-usually assumes the trans conformation. The cis conformation is energetically less stable due to steric interference. ~10% proline residues in proteins follow a cis peptide bond.

Secondary Structure---a-helix

- often right-handed


- 3.6 amino acid residues per turn


-H-bond formation is maximized and is between the carbonyl O of the Nth residue and the –NH group of the (N+4)th reside.


- core of the helix is tightly packed, and its atoms are in van der Waals contact.


-Average length: ~12 residues, 18Å

Secondary Structure---b-sheets

-an extended conformation with a two-residue repeat distance of 7Å


-H bond formation is maximized and is between adjacent polypeptide chains.


-Anti-parallel b-sheet ---polypeptides have opposite N→C orientations.


-Parallel b-sheet ---polypeptides have the same N→C orientation.

Secondary Structure---b-sheets

-R groups extend on opposite sides of a b-sheet.


-An average of 6 residues (up to 15) per strand and an average of 6 strands per sheet.


-b-sheets are pleated.


-b-sheets may contain 2-22 polypeptide strands.

Non-repetitive Structures

Regions of polypeptide that are not characterized by repetitive structures. The structure is irregular, but not random.

b-bend (reverse turns)

A sharp hairpin turn over 4 amino acid residues, frequently connecting adjacent strands of b-sheet. H-bonds are often formed between residues 1 and 4. Residue 2 and 3 are often proline and glycine, respectively.

--loops

Loops of 6-16 residues connect other secondary structures. Frequently found on the surface of protein, these loops may play important roles in biological recognition processes.

Fibrous Proteins

-a single type of secondary structure and often elongated.


-repeating sequences.


-The higher order structures are often stabilized by covalent bonds.


-strong, important for structural proteins that have protective, supportive, or connective roles.


-Commonly insoluble, extracellular proteins.

Keratins

-Principle components of the vertebral epidermal layer and related appendages.


-a-keratin --- in mammals


- The secondary structure is mostly a helix. Two helices twist around each other to form a left-handed coil.


– The central segment of each polypeptide chain has a 7-residue pseudorepeat, a-b-c-d-e-f-g, with nonpolar residues commonly found at positions a and d. Coiled coils are stabilized by hydrophobic interactions. – Dimers associate with each other to form higher order structures.


– Keratin is rich in cysteine residues, which form disulfide bonds to crosslink adjacent polypeptide chains. – “Curled” conformation can be relaxed by treating with reducing agents - b keratin---in birds and reptiles. The secondary structure is b sheets.

Collagen

-Abundant structural proteins of animals, forming strong, insoluble fibers in connective tissues.


-Rich in glycine, proline, hydroxyproline and hydroxylysine.

Globular Proteins

-“typical” proteins---enzymes, antibodies, hormones, etc.


-Secondary structures can be represented by ribbon diagrams: a helix as coiled ribbon, b sheet as flat ribbons, and irregular structures as turns and loops.


- Globular proteins have tightly packed globular structures. Hydrophobic residues are in the interior, while hydrophilic residues are generally on the surface of proteins.

X-ray crystallography

– Purify a protein and crystalize it. Use X-rays to obtain the diffraction pattern of electrons. The diffraction pattern allows the electron density map of the protein to be constructed.


– Most protein crystal structures are less than atomic resolution.


– Most crystalline proteins maintain their native conformations.

NMR Spectroscopy

-An atomic nucleus resonates in an applied magnetic field in a way that is sensitive to its electronic environment.


– A protein's conventional (one-dimensional) NMR spectrum is crowded with overlapping peaks. This problem is addressed by two-dimensional (2D) NMR spectroscopy, which yields additional peaks arising from the interactions of protons that are less than 5 Å apart.


– Interatomic distance measurements, along with knowledge of the protein's sequence and known geometric constraints are used to compute the protein's three-dimensional structure.

Side Chain Location Varies with Polarity

• Nonpolar residues (Val, Leu, Ile, Met, and Phe) occur mostly in the interior of a protein.


• Charged polar residues, Arg, His, Lys, Asp, and Glu are usually located on the surface of a protein.


• Uncharged polar residues, Ser, Thr, Asn, Gln, and Tyr are usually on the protein surface but also occur in the interior of the molecule.

Quaternary Structures

-The spatial arrangement of multiple subunits of a protein.

Why multi-subunits?

-Fewer errors in making several smaller peptides than a big one.


– Errors that do occur can be fixed by replacing a subunit rather than the entire protein.


– For enzymes, each unit can have an active site. – The subunit construction of enzymes provides the structural basis for allosteric regulation.

Subunits Are Symmetrically Arranged – Rotational symmetry

-Cyclic symmetry


– Dihedral symmetry


– Other types of rotational symmetry: tetrahedron, cube, and icosahedron, etc.

Structural Bioinformatics

-Tools for storing, visualizing, and comparing protein structural information


- The Protein Data Bank (http://www.rcsb.org) is the repository for structural information on proteins, nucleic acids, and carbohydrates.


- Molecular graphics programs show macromolecules in three dimensions.


– PDB file format.


– Swiss-PDB Viewer is a powerful program (free) for visualizing three dimensional structures of macromolecules. http://spdbv.vital-it.ch


- Structure comparisons can reveal distant evolutionary relationship

Protein Stability:


Forces important in stabilizing native conformation of proteins:

-Hydrophobic effect is the major determinant of protein structure.


- Electrostatic interactions


– van der Waals forces in the interiors of proteins are an important stabilizing influence. – Both hydrogen bonds and ionic interactions contribute little to protein stability.


• Chemical cross-links


– Disulfide bonds can be an important stabilizing force for extracellular proteins. They are uncommon in intracellular proteins due to a reducing environment.


– Metal ions---internally cross-link proteins. For example, zinc fingers.

Protein Stability:


Protein destabilizing factors:

-Heat


– Extreme pH


– Detergents


– Chaotropic agents---urea and guanidinium ions.

Protein Folding Pathways

-Protein folding is not a random process. Rather a protein folds into its native structure via a hierarchical pathway.


- At every stage along the folding pathway, the protein is stabilized by a decrease in free energy due to the formation of multiple noncovalent interactions.


- A protein folds from a high energy, high entropy state to a low energy, low entropy state---The folding funnel.

Protein Folding in Vivo

Proteins usually fold much more quickly in vivo than in vitro, leading to the discovery of specific proteins that aid in the folding process in vivo.

Protein disulfide isomerases

-catalyze the reversible reduction/oxidation of disulfide bonds. Also able to catalyze the initial disulfide bond formation

Molecular chaperones

(1) bind to newly synthesized proteins and facilitate protein folding.


(2) bind to unfolded and partially unfolded proteins to prevent non-native folding as well as polypeptide aggregation and precipitation, and to refold proteins


(3) help proteins unfold in preparation for their transport through a membrane and to refold them afterwards.

The Hsp70 family proteins

highly conserved 70-kD proteins in prokaryotes and eukaryotes. Use ATP hydrolysis to facilitate protein folding. They may require Hsp40 cochaperones.

Trigger factor

a ribosome-associated chaperone in prokaryotes, prevents the aggregation of newly synthesized polypeptides.

The Chaperonins

-multi-subunit proteins, such as GroEL/ES, form closed chambers where proteins fold.

The Hsp90 proteins

in eukaryotes facilitate the folding of proteins involved in cellular signaling.

Protein Misfolding Can Cause Diseases

~ 35 human diseases known as amyloidoses are associated with the extracellular deposition of normally soluble proteins in the form of insoluble fibrous aggregates known as amyloids.


• Amyloid-b protein and Alzheimer’s disease.


Prion diseases are transmitted by the prion form of proteins.


– Mad cow disease, kuru and Creutzfeldt-Jakob disease (CJD). These diseases are known as transmissible spongiform encephalopathies.


• Amyloid fibrils contain b sheet structures.

Protein Dynamics

-The three dimensional crystal structures of proteins do not mean that proteins are static and rigid.


• Flexibility of proteins largely reflects the fact that relatively weak noncovalent forces are the primary stabilizing factors for proteins.


• Rather than a single conformation, a protein’s native structure consists of a collection of rapidly inter-converting conformations.


– Small conformational changes are referred to as breathing, allowing small molecules access to their binding sites.


– Large conformational changes are often induced upon the binding of a ligand, a process called induced fit.


• Structural flexibility of proteins is functionally important.


• Terminology – Ligand – Binding site

Why Study O2 -Binding Proteins?

The importance of O2 binding proteins, myoglobin and hemoglobin.


• The globin family is an excellent example of evolution through gene duplication.


• The primary, secondary, tertiary, and quaternary structures are well-known, and their functions are well-studied and vital to human health.


• They serve as models illustrating structure-function relationships of proteins.


• Studies on these two proteins illustrate how proteins interact with other components of living systems. Most importantly, these proteins illustrate one of the most central aspects of biochemical processes: the reversible binding of a ligand to a protein

The Heme Prosthetic Group

Oxygen is poorly soluble in aqueous solutions and cannot be transported to tissues in sufficient amounts if it is simply dissolved in blood serum.


• Amino acid side chains are not suitable for reversible bindings of O2 . This role is carried out by certain transition metals, such as iron and copper.


• Free iron promotes the formation of highly active reactive oxygen species (ROS) that can damage DNA and other macromolecules. • In multi-cellular organisms, iron often exists in a protein-bound prosthetic group called heme, which has a heterocyclic porphyrin ring containing four pyrrole groups linked by methylene bridges.


• The iron (II) atom is coordinated by four porphyrin N atoms, one N atom from a histidine side chain, and molecular O2 . CO, NO, and H2S can compete with O2 for binding to heme.

Myoglobin

• Myoglobin consists of one polypeptide chain of 153 amino acid residues. Its secondary structure is primarily a-helix.


• Myoglobin has a compact structure, with a hydrophobic interior and a hydrophilic exterior.


• Heme is wedged between helices E and F. Hydrophobic methyl and vinyl groups are oriented toward hydrophobic interior; polar propionate groups are oriented toward the opening.


• Two hydrophobic side chains, Val E11 and Phe CD1, help keep heme in the binding pocket.


• Without myoglobin, iron (II) in the free heme is rapidly oxidized to iron (III), which does not bind O2 .


• Under certain conditions, iron (II) in the heme group of myoglobin can also be oxidized to iron (III) to form metmyoglobin.


• Heme in myoglobin increases binding specificity for O2 . CO binds to free heme more than 20,000 times better than O2 ; but it binds only 200 times better to myoglobin-bound heme than O2 .

O2 Binding Properties of Myoglobin

The fractional saturation of myoglobin, YO2, is defined as the fraction of O2 -binding sites occupied by O2 in myoglobin.


• Myoglobin’s O2 binding curve is defined by the fractional saturation equation:


• The O2 -binding curve of myoglobin (YO2 versus pO2 ) is hyperbola. When YO2 = 0.5, K = pO2 . Thus, K can be defined as p50, the value of pO2 when myoglobin’s O2 binding site is 50% occupied.


• Based on this hyperbola curve, myoglobin is almost fully saturated with O2 within the physiological range of pO2 (100 torr in the arterial blood and 30 torr in venous blood).


• The major physiological function of myoglobin is to facilitate O2 diffusion in muscle cells. MbO2  Mb + O2

Hemoglobin-Structure

• A tetrameric protein with the quaternary structure of a2b2 (a dimer of ab protomers).  a, 141 a.a., 7 a helices; b, 146 a.a., 8 a helices.


• The ab protomers exhibit C2 symmetry. Structural similarity between a and b subunits also results in additional rotational pseudo-C2 symmetry whose axis is perpendicular to that of the exact C2 symmetry.


• Each subunit binds one heme prosthetic group. Four heme molecules per hemoglobin protein.  a and b subunits form extensive contact, involving 35 residues at the a1-b1 (a2- b2) interface and 19 resides at the a2-b1 (a1-b2) interface. Associations are mostly hydrophobic and involve some hydrogen bonds and ion pairs.


• O2 binding induces conformational changes in hemoglobin, rotating one ab protomer ~15o with respect to the other. Oxygenation brings b subunits closer and leads to changes in the interactions at the a2-b1 (a1-b2) interface. This structural change is crucial in hemoglobin’s O2 -binding behavior.

Hemoglobin-O2 binding

Assuming hemoglobin binds n molecules of O2 simultaneously, we have hemoglobin’s O2 association equation: Hb + nO2→Hb(O2 )n . In analogy with that of myoglobin, the fractional saturation of hemoglobin is:


• The O2 binding curve of hemoglobin is sigmoidal. A sigmoidal curve in any binding system is indicative of a cooperative interaction between different binding sites. The value of p50 of hemoglobin is 26 torr.


• The Hill coefficient n is an indicator of cooperativity of ligand binding to a protein. n=1, no cooperativity; n>1, positive cooperativity; n<1, negative cooperativity.


• Hill plot: • For hemoglobin, n is between 2.8 and 3, so hemoglobin’s O2 binding is highly, but not infinitely, cooperative. The maximum value of n is the number of subunits in a multisubunit protein.

Hemoglobin---Mechanism of Cooperativity of O2 Binding

Hemoglobin has two conformational states, T (tense) and R (relaxed).


• In the T state, Fe(II) sits ~0.6 Å out of the heme plane. Upon O2 binding, Fe(II) moves into the center of heme, dragging covalently linked His F8 ~ 0.6 Å towards the heme plane. The F helix tilts and translates by ~1 Å across the heme plane.


• The changes in the tertiary structure of hemoglobin are coupled to the shifting of the a2-b1 (a1-b2) interface from one stable conformation to another.


• The T state is stabilized by a network of intra- and inter-subunit ion pairs and H bonds among the C-terminal residues of subunits. These networks are broken during the T→R transition.


• The subunits of hemoglobin are so tightly coupled that large tertiary structure changes within one subunit do not occur without changes of the quaternary structure

The Bohr Effect and Transport of CO2 and O2

-Increasing pH induces hemoglobin to bind more O2 . Conversely, O2 binding to hemoglobin releases protons bound in hemoglobin (~0.6 proton released/O2 binding).


-CO2 also binds to hemoglobin by forming carbamate with the N-terminal amino groups of blood proteins. R-NH2+CO2 R-NH-COO- + H+ . The T form preferentially binds CO2 to form carbamate, which helps unload O2 in the tissues and transport CO2 out. Released protons due to carbamate formation help unload even more O2 through the Bohr effect.

Physiological functions of the Bohr effect

-Facilitate O2 unloading in tissues. Respiration generates CO2 , which is converted to bicarbonate and protons. More protons favor the T state of hemoglobin and increase O2 unloading.


– Facilitate CO2 transport to lungs from tissues. Proton uptake by hemoglobin favors bicarbonate formation in the capillaries. Bicarbonate is then circulated back to lungs. In lungs, O2 binding to hemoglobin releases protons, which react with bicarbonate to produce CO2 . CO2 is then exhaled.


– The Bohr effect helps deliver more O2 in highly active muscles. These muscles produce lactic acid, which lowers pH. Lower pH unloads more O2 in such muscles.

BPG (D-2,3-bisphosphoglycerate) and O2 Transport

-Highly purified hemoglobin binds O2 much more tightly than hemoglobin in whole blood. This is partly due to the absence of bisphosphoglycerate in purified hemoglobin.


• BPG preferentially binds to deoxyhemoglobin. BPG stabilizes the T form by forming ionic interactions with hemoglobin in the central cavity of hemoglobin.


• An increased synthesis of BPG helps human adapt to high altitude by reducing hemoglobin’s affinity for O2 .


• BPG helps deliver O2 to fetus. Fetal hemoglobin (a2g2) has lower affinity for BPG due to the substitution of His143 in the b subunit with serine residue in the g subunit. Higher affinity of fetal Hb for O2 facilitates O2 delivery to the fetus.

Allosteric Proteins and Models for Cooperative Ligand Binding

Ligand binding to one site of a protein affects the binding of another ligand to another site. This effect is termed allosteric interaction. Allosteric effects generally require interactions among subunits of an oligomeric protein.

Symmetry model

An allosteric protein is an oligomer of structurally identical or similar subunits


– Each oligomer exits in two conformational states, T and R.


– The ligand can bind to subunit in either conformation. Only the conformational change affects the affinity for the ligand.


– Conformational changes in different subunits take place simultaneously. Thus, the structural symmetry of the protein is preserved.


– Limitation: It does not account for negative cooperativity.

Sequential model

Ligand binding induces a conformational change in the subunit to which it binds. Conformational changes do not occur symmetrically.


– Cooperativity arises through the influence of those conformational changes on the binding affinity (can be either stronger or weaker) for the ligand in neighboring subunits.


-Ligand binding induces a conformational change in the subunit to which it binds.


-Conformational changes do not occur symmetrically.

Hemoglobin and Human Health

Mutations in hemoglobin can lead to clinical symptoms and diseases including hemolytic anemia, cyanosis, and polycythemia.

Sickle-cell disease

Sickle-cell hemoglobin (HbS)---The mutation of Glu 6 of the b subunit to Val.


– Red blood cells of sickle cell disease patients assume a sickle shape upon deoxygenation. These sickle-shaped cells are trapped in capillaries and lead to a block of blood flow to certain tissues.


– In the structure of deoxyhemoglobin, Val side chain in each of the HbS tetramer nestles in a hydrophobic pocket created by Phe85 and Leu88 of b subunits in a neighboring HbS tetramer.


– The hydrophobic pocket does not accommodate the side chain of wild-type glutamic acid residue. Oxyhemoglobin does not have this hydrophobic pocket, either. This is the reason why hemoglobin S fibers do not exist in arterial blood.


– Many homozygous HbS patients only show a mild form of sickle-cell disease by expressing high levels of fetal hemoglobin.

HbS confers resistance to malaria. Malaria is caused by mosquito-borne protozoan Plasmodium falciparum, which resides in red blood cells during much of its 48-hour life cycle.

Plasmodia lowers pH inside the red blood cells by ~0.4 units. The lower pH favors the deoxyhemoglobin via the Bohr effect, thereby increasing sickling in red blood cells that contain HbS. Thus, plasmodia-induced sickling allows infected cells to be removed by spleen in the early stages of malarial infection.

Antibodies

Each immunoglobulin (Ig) has at least two identical light chains (L, ~23 kD) and two identical heavy chains (H, 53~75 kD). The subunits of Ig associate by disulfide bonds and noncovalent interactions to form a Y shaped molecule with the formula (LH)2 .


– Five classes of Ig differ in the type of heavy chain they contain: IgA, IgG, IgD, IgE and IgM.


– Both L and H subunits of Ig have a variable region and a constant region. The variable regions of Ig molecules determine the binding specificity for an antigen.


- Antibody diversity results from gene rearrangement and mutations.


– Monoclonal antibodies can be generated using hybridoma technology.


Monosaccharides

aldehyde or ketone derivatives of linear polyhydroxy alcohols (>= 3C).


Monosaccharides

The chemical nature of the carbonyl group---Aldose (aldehyde) and ketose (ketone)


– The number of carbon atoms: triose, tetrose, pentose, hexose, etc.


– Stereoisomers: D versus L


– Important aldoses---glyceraldehyde, ribose, glucose, mannose, galactose. Dglucose and D-galactose are epimers of each other with respect to C4; Dglucose and D-mannose are epimers of each other with respect to C2


– Important ketoses---dihdroxyacetone, ribulose, fructose.

Monosaccharides

Intramolecular reactions between -C=O and hydroxyl groups produce cyclic structures – Sugars with a 6-membered ring are called pyranose – Sugars with a 5-membered ring are called furanose

Monosaccharides

Cyclic sugars have two anomeric forms---The carbonyl carbon of a cyclic sugar is called the anomeric carbon.  a anomer---The –OH group is on the opposite side of the sugar ring from the – –CH2OH group at the chiral center that defines the D or L configuration.  b anomer--- The –OH group is on the same side of the sugar ring from the – CH2OH group at the chiral center that defines the D or L configuration.

Monosaccharides

Sugar derivatives – Oxidation of the aldehyde group of aldose yields aldonic acid, e.g., D-gluconic acid – Oxidation of the primary alcohol group of aldose produces uronic acid, e.g., D-glucuronic acid – Reduction of aldoses and ketoses produces polyhydroxy alcohols, e.g., ribitol (component of flavin coenzymes), glycerol and myo-inositol (lipid components). – Replacement of a –OH group with H yields deoxy sugars, e.g., b-D-2-Deoxyribose (the sugar component of DNA’s sugar-phosphate backbone) – Replacement of one or more –OH with an amino group produces amino sugars, e.g., Dglucosamine and D-galactosamine. – N-acetylneuraminic acid---derived from N-acetylmannosamine and pyruvic acid. Nacetylneuraminic acid is an important component of glycolipids and glycoproteins. Nacetylneuraminic acid and its derivatives are often known as sialic acids.

Glycosidic bonds

The anomeric group of a sugar can condense with an alcohol to form a- and b-glycosides, which are cyclic acetals or ketals. The bond connecting the anomeric carbon and the alcohol O is called a glycosidic bond. An N-glycosidic bond is formed between an anomeric group and an amine.

Reducing and non-reducing sugars

Saccharides bearing a –OH attached to anomeric carbon are reducing sugars; saccharides whose anomeric carbon lacks an a –OH group are nonreducing sugars

Polysaccharides-Glycans

Polymer of monosaccharides linked by glycosidic bonds. A full description of a oligo- or polysaccharides includes the identities, anomeric forms, and linkages of all of its component monosaccharide units.


• Disaccharides – Lactose----O-b-D-galactopyranosyl-(1→4)-D-glucopyranose – Sucrose----O-a-D-glucopyranosyl-(1→2)-b-D-fructofuranoside, an nonreducing sugar.

Structural polysaccharides: cellulose and chitin

Cellulose---Structural component of plant cell walls. It is a linear polymer of up to 15,000 Dglucose residues linked by b(1→4) glycosidic bonds. The strength of cellulose fibers is partially due to H-bonding between individual strands. – Chitin---The principle structural component of the exoskeletons of crustaceans, insects, fungi and algae. It is a polymer of b(1→4) linked N-acetyl-D-glucosamine residues.

Storage polysaccharides: starch and glycogen

Starch---Principle energy reserve of plants. It consists of a-amylose and amylopectin.  a-amylose---linear polymer of glucosyl units linked by a(1→4) glycosidic bonds. • Amylopectin--- a(1→4) linked main chains with a(1→6) branch points every 24-30 glucose residues. – Glycogen---storage saccharides in animals, structurally similar to amylopectin but more branched with a(1→6) branch points every 8-14 glucose residues

Glycosaminoglycans

unbranched polysaccharides consisting of alternating uronic acid and hexosamine residues. They are highly viscose and elastic, making them prefect lubricants and shock-absorbers.



Hyaluronic acid--- b(1→4) linked disaccharide units consisting of b(1→3) linked Dglucuronate and N-acetyl D-glucosamine.


– Heparin---polymers of sulfated disaccharides, exists in mast cells that occur in arterial walls, important in inhibiting blood clotting.


– Other glycosaminoglycans include chondroitin, dermatan, and keratan sulfate.

Glycoproteins

Proteins containing carbohydrates, important for extracellular matrix, bacterial cell walls, enzymes, hormones, receptors, etc.

Proteoglycans:

Important component of extracellular matrix, especially cartilage. Have a bottle brush-like architecture with “bristles” (up to 100) noncovalently attached to a strand of hyaluronic acid “backbone” (0.4-4mm). Bristles consist of a core protein to which glycosaminoglycans attach via glycosidic bonds to side chain O atoms of specific Ser and Thr residues. Smaller oligosaccharides are glycosidically linked to the core protein via the amide N of specific Asn residues. – Proteoglycans confer cartilage the property of high resilience.

Peptidoglycans

component of bacterial cell walls. The enzymes responsible for their synthesis are targets of some antibiotics. Polysaccharide strands (linear chains of alternating b(1→4) linked N-acetylglucosamine and N-acetylmuramic acid) cross-linked by oligopeptides. Oligopeptides contain D-amino acids and isopeptide bonds, which make them resistant to proteases.

Glycoproteins

Secreted and membrane-associated proteins of eukaryotes are usually glycosylated. • N-linked oligosaccharides – N-acetylglucosamine is invariably b-linked to the amide N atom of the side chain of Asn residues in the sequence Asn-XSer/Thr, where X is any amino acid except Asp or Pro. – Attachment occurs cotranslationally. Addition of a 14-residue (mannose)9 (glucose)3 (GlcNAc)2 oligosaccharide is followed by trimming and addition of sugar residues. The final composition of oligosaccharides depends on the identity of the target protein and the particular enzyme ensemble of the cell.

O-linked oligosaccharides

The O-glycosidic attachment typically involves the disaccharide core b-galactosyl-(1→3)-a-N-acetylgalactosamine attached to the OH group of either Ser or Thr.


– Attachment occurs post-translationally, inside the Golgi apparatus. Signals for O-linked glycosylation are not specific sequences. Rather, O-glycosylation sites are specified by the secondary and tertiary structure of proteins.

Oligosaccharides Determine Glycoprotein Structure, Function, and Recognition

Structural functions


– Restrict access to the surface of a protein.


– Help proteins fold into their native state.

Targeting signals

Lysomal proteins contain Nlinked oligosaccharides with mannose-6-phosphate residues. A mannose-6-phosphate receptor in the Golgi apparatus selects proteins for transport to lysosomes.

Mediate cell-cell recognition events

-Cells are coated with glycoconjugates such as glycoproteins and glycolipids. Lectins (proteins that bind carbohydrates) on the surface of cells can recognize individual monosaccharides in particular linkages to other sugars in an oligosaccharide. Examples include sperm-egg recognitions during fertilization and interactions between cell-surface carbohydrates and virus, bacteria or parasites during their invasion of target tissues.


• Influenza virus binds to sialic acid residues present on cell-surface glycoproteins. Tamiflu inhibits sialidase (neuraminidase).

Antigen determinants

The carbohydrates on cell surfaces are some of the best known immunochemical markers, e.g., the ABO blood group antigens.