of
Biochemistry
Third Fundamentals Edition
Donald Voet Judith G. Voet
Charlotte W. Pratt
Chapter 6
Proteins: Three-Dimensional Structure
Copyright 2008 by John Wiley & Sons, Inc.
Tropomyosin tail (portion)
-keratin
Collagen
The collagen fold is described by a set of values of
and which result in a twisted helix. In the collagen
triple helix, three twisted helices wrap around each
other.
The unique structure of the collagen fold results from
the repeating amino acid sequence gly-X-pro- or -glypro-Y-.
The synthesis of the individual collagen chains involves
several posttranslational modifications: hydroxylation of
prolines and lysines, glycosylations, disulfide bond
formation, proteolytic processing, lysine oxidation, and
crosslinking. Defects in any of the enzymes for these
modifications results in a connective tissue deficit.
Inherited defects cause Ehlers-Danlos syndromes.
Vitamin C deficiency compromises hydroxylation by
prolyl and lysyl hydroxylase (scurvy), and selenium
poisoning crosslinking compromises by lysyl oxidase
(lathyrism).
The Anfinsen Experiment
Ribonuclease can be unfolded by addition
of beta-mercaptoethanol and urea with
complete loss of enzymatic activity and
then refolded with complete restoration of
activity.
The order of removal of urea and betamercaptoethanol is critical for recovery of
activity.
Prion Diseases
Scrapie, bovine spongiform encephalopathy, kuru, Creutzfeld-Jakob disease,
Gerstmann-Straussler syndrome, fatal
familial insomnia are all prion diseases.
Transmission involves no nucleic acids,
but rather infection with a distinctive
conformation of the prion protein.
The pathological form of the prion protein,
PrPSc, and the normal form, PrPC, differ
only in conformation.
PrPSc is highly insoluble, resistant to
proteolysis, and aggregates to form
amyloid plaques. PrPC is soluble and is
rapidly degraded by proteolysis.
PrPC can be converted to PrPSc by an
associative process, which may involve an
accessory chaperone protein.