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15 Cards in this Set
- Front
- Back
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What happens to proteins after translation?
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Not all work in the cytoptlasm(proteins)
They get integreated in membrane Get trafficed to different places Today: Have to fold to correct shape folidng in vito POST TRANSLATIONAL modifications: very important Regulation and processes Turn over: not all proteins fold; deal with the problem. Machine that degreades proteins that are not folded correctly; will chop it up and rem ake a new chain |
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Ideas from the early days
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Anfinsen's winning experiment:
Important: small protein ribo nuclease Isolatefrom cells; chews up rnas Isolate these, put in test tube, denatrue them so that it’s a long strand, and unfoldeid portein does not stay active reversed the step; wash out the denaturing buffer, put it back in good aqueous solution and would fold back to be active |
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in vivo: protein folding in a crowded cell
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cells packed with rnas and dnas and proteins : cell wants a single chain to bury its hydorphobs
At high concentrations, and denatured proteins, the problem with renaturing is that it might hook up with another chain=cross linked and wont fold to well definted shape of phobic inside |
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in vivo: co translational folding
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some proteins are big and require long time to synthesize
deals with what is has when it comes out and can easily be trapped in misfolded structures: collapses on itself (red and blue domain all mixed-up) |
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Pathways that help fold proteins in vivo
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Trigger factor:Hsp70 and 60 recognize and bind to exposed hydrophobic patches of unfolded proteins
Properly has phillic on surface; so if you want to recongize a poten misfolded protein, look for phobic proteins search for phobobic and binds it prevents from it folding, and CHAPERONS the phobic residues and prevents from folding with others MISFOLDED PROTEINS SIGNATURE = PHBOIC PATCHES; AND THOSE HELPING EVOLVED TO RECOGNIZE THEM AND BIND THEM AND INTERACT WITH THEM TO AVOID PHOBI PHBOIC INTERACTIONS BETWEEN TWO MISFOLDED CHAINS |
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Chaperones
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Hsp70 and 60: "heat shock proteins" during stress help out
if two phobic batches come together they form an insoluble mass and suck up resources |
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Hsp70 Family
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ATP ase domain Atpase domain
Atp binds, one confo change; has ablibity to hyrdroplize atp--> adp -->confo change--> affects porteins Specializes with recognizing and interactinve with phobic patches |
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Hsp70 Function
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Atp bound form looks for the patches, and will bind and unbind. No strong affinity. Help of accessory protein, whena tp bound it helps stimulate hydrolysis of atp to adp, and thus a confo change and effectively clamps onto phobic patch
Chain is coming off ribosome, not fully produced, preventnng it from tring to fold in early state. Needs to wait till entire chain is done to fold |
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Hsp60 Family
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"barrel"
repeating units forming a hexamer 10% of proteins interact with this family also recog phobic patches: atp dependent |
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Hsp60 Function
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Hydrophobic residues on inside wall
Exposed patches will interact with residues on wall Induces c. change, and you swap so phillic are inside, and phobic residues are no longer visible and excessible Look watery now What if it hadnt correctly folded. The green still insde, go back to first confo, phobic bind with it, cap goes on, stretch it and give another chnace |
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Some mis-folded proteins can't be saved
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cycles that keep getting misfolded proteins : will be chopped up by proteasome
turn back into an amino acid rather than keep it around and waste more energy |
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Proteasome
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Recognzze those that are targeted for degration, uses atp and strethces polymer, and inside the pretease acts like scissors choping it up
similar to hsp60 with structure |
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Ubiquitination
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small protein: 70 AAs
attached to amino group of Lys side chain w/ pep bond mark proteins for degration by proteasome the KISS OF DEATH that targets the proteins; if you have a lot of ubiitins on you the protease will target you and chop it up C-terminus of ubiquitin attaches to the end of they lysine side chain Doenst just attach to misfolded proteins multiple signals of ubiquitin marks |
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E3 ligases ubiquitinate target proteins
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Ubiquitin attached to E1 ligase;Transferred to E2 ligase;Many different E3 ligases, each recognize specific proteins
E1= uses atp and makes a high energy bond; ubiquitin ready to be put on something Intermidedate step: e2 works with e3’s who recongize somehting (misfolded, or a phophorylatino mark for regulation) E3 catalyzes transfer of charged ubquitin onto lysin on it ex: uses mislfoded, and swaps adds ubiquitein chain E3 IS MOST IMPORTANT GUYS E3 DOESN’T ATTACH TO UBIITITN, recongiznes and causes reation |
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Protein modifications: phosphorylation
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AA that go through this have an OH GROUP
Kinases take atp and phophate group and make an OP: negatively charged FAST AND REVERSIBLE regulate conformation: can activate and inactivate add a negative group has consequences on protein structure: confo chage and goes into a configuration so it begins to interact with diff things |
