The alphabet of intrinsic disorder: II. Various roles of glutamic acid in ordered and intrinsically disordered proteins

Uversky, Vladimir N

Glutamic acids in intrinsically disordered chaperones. The high content of glutamic acids in artificial EBDs designed as solubilization means was chosen because of the earlier observation that proteins with high net charge densities can function as effective intra-and intermolecular chaperones. 169-172 For example, polyglutamate among other polyanions was shown to act as a chaperone and to accelerate the in vitro refolding of the Arc repressor protein. 173 Small heat shock proteins (HSPs) have flexible C-terminal extensions that, although variable in length and sequence, are rich in acidic amino acids. 169 The sHSP α-crystallin can act as a chaperone on the fibroblast growth factor 1 (FGF-1), and this chaperone action is mediated by electrostatic interactions between the basic regions of the growth factor and acidic regions of α-crystallin. 174 Nucleolar chaperone B23 (294 residues, 31 of which are glutamic acids) has two acidic regions (residues 120-132 and 161-188) that contain 8 glutamic residues each and that are necessary for the B23 chaperone-like activity. 175 Tubulin has chaperone-like activity being able to suppress the aggregation of soluble lens proteins, equine liver alcohol dehydrogenase, malic dehydrogenase and insulin, but only if its acidic C-terminus (that contains 39% and 33.3% of glutamic acid residuess in the porcine αand β-tubulins, respectively) was intact. [176] [177] [178] Many polyanionic propeptides were shown to serve as intramolecular chaperones to aid folding of the respective proteins. [179] [180] [181] [182] For example, propeptides of human neutrophil defensins contain up to 15.8% glutamic acids. Also, the C-terminal solubilizing domain of human α-synuclein (residues 100-140) contains 24.4% glutamates, whereas ERD10 (260 residues) and ERD14 dehydrins (185 residues) from Arabidopsis thaliana contain 19.6% and 21.1% glutamic acids respectively. Some functions of glutamate-rich peptides. This section presents several illustrative examples of important biological functions attributed to glutamate-rich peptides.