Protein Life Structure Flashcards
Where does protein folding start?
- Proteins begin to fold while they are being synthesized on the ribosome
- As portions of newly synthesized proteins are emerging from ribosome, many AA residues involved in secondary and tertiary structure become available to interact w/ ea other
Molten Globule
- initial form that many globular proteins attain ad they begin to fold
(This is not its final folded state and proteins in this meta-state are unlikely to be active)
Molecular Chaperones
- Transition from molten globule —> final folded protein is not efficient and requires aids
- members of heat shock family of proteins that participate in protein folding reactions and reduce/prevent protein aggregation
- named by weight
- actions require ATP
Proteasome-Dependent Protein Degradation Pathway
- 19S cap serves as entry site and unfolds proteins via ATP hydrolysis
- then sent to 20S core for proteolysis
Proteasome
- large multi-sub unit abundant machine that degrades targeted proteins in an ATP-dependent manner (IN CYTOPLASM)
- 20 S core is segment where proteolysis occurs
- 19 S cap is regulatory center of proteasome
Ubiquitin
- 76 AA protein that is covalently attached to specific lysine residues on target proteins through its carboxyl terminus
- Need a polyubiquitan chain (min chain length of 4 ubiquitin) on targeted proteins
E1
Ubiquitin-Activating Enzyme
- uses ATP hydrolysis to “activate ubiquitin” by creating a covalent attachment of ubiquitin to specific -SH group on E1
- Least common
E2
Ubiquitin-Conjugating Enzyme
-interacts w/ E1 leading to the transfer of ubiquitin to a specific -SH group on E2
More rare than E3
E3
-Ubiquitin Ligase
- Ubiquitin-charged E2 forms a complex w/ an E3
(In some cases the ubiquitin is transferred from E2 to E3)
-Most abundant
Final Steps of Ubiquitin Path
- 1- Distinct E3 recognizes the “degradation signal” on target protein
- “Degradation signal”- specific stretch of AA
- Target protein is now bound to E2/E3 complex
- 2- Ubiquitin is transferred from E2 (or E3) —> specific lysine residue on target protein forming a covalent bond
- 3- Process is repeated as additional ubiquitin molecules are linked to specific lysine residues on protein-linked ubiquitin via a covalent bond
- Result= targeted protein contains covalently-attached multi-ubiquitin chain
SRP
- multi-subunit RNA protein particle; soluble cytoplasmic protein
- recognizes signal sequence of growing polypeptide as it emerges from ribosome —> arrest in protein translation (PAUSE)
- SRP-bound to the signal sequence and ribosome then interacts w/ SRP receptor on outer membrane of ER —> transfer of translating protein to translocation machinery
BiP
- chaperone protein that binds unfolded segments of polypeptide as they emerge into ER lumen
- ATP driven cycles of binding and releasing BiP acts to pull translocating protein into ER lumen
Co-translation Transport Into ER
-Import of proteins to rough ER occurs B/F synthesis is complete (co-translation transport)
1- signal sequence (hydrophobic) on polypeptide chain is recognized by SRP as it leaves ribosome
2-SRP-signal sequence interact w/ SRP receptor on outer ER membrane
3- translating protein moved to translation machinery
4-Once ribosome docks on translocation channel protein … translation resumes and translocation into ER begins as translocation channel opens
“start” and “stop” transfer sequences
Hydrophobic and responsible for transmembrane insertion of
- Start transfer sequence- ER signal sequences that interact w/ translocation machinery itself by opening translocation channel and beginning transport into ER
- Stop transfer sequence- hydrophobic; on translocating proteins; recognized by specific components of translocation machinery
Where are start and stop transfer sequences found?
-Both are found on the translated protein itself
