BIOLOGY 2B03 Lecture Notes - Lecture 3: Covalent Bond, Lysine, Atp Hydrolysis
6 Jun 2018
School
Department
Course
Professor
Protein Structure and Function
Correcting Misfolding: Chaperones
most protein molecules fold rapidly into their correct configuration •
incompletely folded proteins are helped to fold by chaperone proteins •
misfolded proteins are recognized for degradation - to prevent inappropriate interactions + aggregates •
General principle: to prevent inappropriate interactions between amino acid residues and increase the efficiency •
of protein folding
There are two types of chaperones
both help proteins fold properly, not necessarily fold for them •
Monomeric Molecular Chaperones
heat-shock proteins (HSP) •
expressed at high levels in conditions of stress ◦
contains nucleotide-binding domain and ◦
substrate-binding domain
Ex. HSP70 in cytosol and mitochondria ◦
Ex. BiP in ER ◦
Ex. DNAk in bacteria ◦
hydrophobic patch on unfolded protein is a cluster •
of hydrophobic AA residues exposed to cytosol
bind to hydrophobic R groups and prevent PP from •
associating with other proteins or folding premature
+ prevents aggregation with other hydrophobic
residues
Chaperonins
these are large cylindrical macromolecules assemblies •
that form an isolation chamber for newly synthesized
polypeptides that allows them to fold without
interference from other macromolecules
TCiP - cytosol ◦
GroEL - bacteria/chloroplast ◦
Hsp 60 - mitochondria ◦
they form forming chambers •
consist of 2 large subunits (GroES + GroEL) ◦
Chaperonin chamber enlarges upon cap binding
conformational changes are seen in GroEL upon •
association with GroES
GroEL shifts to larger 'relaxed' conformation when associated with •
GroES, releasing protein within chamber
tight conformation is GroEL w/o GroES ◦
each Hsp60 protein changes shape to change shape of GroEL chamber •
individual behaviour of subunits lead to overall chaperone function ◦
Protein Degredation
cells must degrade •
misfolded proteins ◦
denatured proteins ◦
proteins at too high a concentration ◦
Document Summary
Correcting misfolding: chaperones most protein molecules fold rapidly into their correct configuration incompletely folded proteins are helped to fold by chaperone proteins misfolded proteins are recognized for degradation - to prevent inappropriate interactions + aggregates. General principle: to prevent inappropriate interactions between amino acid residues and increase the efficiency of protein folding both help proteins fold properly, not necessarily fold for them. Monomeric molecular chaperones heat-shock proteins (hsp) expressed at high levels in conditions of stress contains nucleotide-binding domain and substrate-binding domain. Dnak in bacteria hydrophobic patch on unfolded protein is a cluster of hydrophobic aa residues exposed to cytosol bind to hydrophobic r groups and prevent pp from associating with other proteins or folding premature. Chaperonins these are large cylindrical macromolecules assemblies that form an isolation chamber for newly synthesized polypeptides that allows them to fold without interference from other macromolecules. Hsp 60 - mitochondria they form forming chambers consist of 2 large subunits (groes + groel)
