BMB170c_2011_04_12_LECTURE

BMB170c_2011_04_12_LECTURE - BMB 170C Chaperones What is a...

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Unformatted text preview: BMB 170C Chaperones What is a chaperone? Thanks to Aaron Chamberlain for sharing slides Protein Fates Review: Hartl (2002) Science 295:1852 In vivo folding • Cell cytosol is crowded – [protein] is ~340 mg/ml – [ribosome-bound chains] in E. coli is ~35 µM but locally more concentrated in polysomes • Folding is typically co- translational – C terminal 30 aa buried in ribosomes – Nascent chains must remain unfolded until entire domain has emerged – Translation ~10aa/sec >> very slow McGuffee & Elcock (2010) PLoS Comp Biol Folding paths Review: Hartl (2002) Science 295:1852 Molecular chaperones • A group of unrelated classes of proteins – Bind to and stabilize an unstable conformation – Facilitates correct fate in vivo – Aren’t part of the final structure • Possible correct fates – Folding, oligomeric assembly, transport to organelle, disposal by degradation • Molecular chaperones don’t violate Anfinsen’s self assembly principle – No inherent information in chaperone about proteins final fold – Prevent incorrect interactions within and between non-native proteins – Assist self-assembly – Increase the yield but not the rate (except for isomerases) Basic idea Chaperones Protein folding Subunit assembly nucleosome Specific folding barrier reduction General misfolding reduction Protein Disulfide Isomerase (PDI) Peptidyl proline cis-trans isomerase (PPI) Nascent chain binding proteins.-Trigger factor (TF).-DnaK, DnaJ. Cylindrical folding/unfolding structures.-Gro EL/ES in E. coli . Families of Chaperones Small heat shock proteins (hsp25) * protect against cellular stress * prevent aggregation in the lens (cataract) Hsp60 system (cpn60, GroEL) ATPase * protein folding Hsp70 system (DnaK, BiP) ATPase * stabilization of extended chains * membrane translocation * regulation of the heat shock response Hsp90 ATPase * binding and stabilization/ regulation of steroid receptors, protein kinases Hsp100 (Clp) ATPase * thermotolerance, proteolysis, resolubilization of aggregates Calnexin, calreticulin * glycoprotein maturation in the ER * quality control Folding catalysts: PDI, PPI [folders] 3 Main Families • Conserved across kingdoms • Discovered because of heat shock induction – Also induced from other stresses resulting in accumulation of unfolded proteins • Majority expressed constitutively – essential for cell growth Plan • Hsp60 family – GroEL/ES (Hsp60) – TriC and thermosome • Hsp70 family – Activators • Hsp90 • sHsps • Hsp100 • Trigger factor • Prefoldin • Folding catalyzers – disulfide isomerases (DsbA) – Prolyl isomerases • Targeting factors – SecB – SRP – REMPs – Get3 Cytoplasmic Chaperone Summary Hartl 2002 Science Hsp60 family of proteins Location Chaperone Roles Prokaryotic cytosol GroEL/ GroES Protein folding, including elongation factor, RNA polymerase. Required for phage assembly Mitochondria/ Chloroplasts Hsp60/10 Cpn60/10 Folding and assembly of imported proteins...
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This note was uploaded on 01/03/2012 for the course BI 170c taught by Professor List during the Fall '09 term at Caltech.

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BMB170c_2011_04_12_LECTURE - BMB 170C Chaperones What is a...

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