title: Dimerization by domain hybridization bestows chaperone and isomerase activities.
abstract: Thioredoxin, DsbA, the N-terminal active-site domain a and the non-active-site domain b of protein-disulfide isomerase are all monomeric with a thioredoxin fold, and each exhibits low or no isomerase and chaperone activity. We have linked the N terminus of the above four monomers, individually, to the C terminus of the N-terminal domain of DsbC via the flexible linker helix of the latter to produce four domain hybrids, DsbCn-Trx, DsbCn-DsbA, DsbCn-PDIa, and DsbCn-PDIb. These four hybrid proteins form homodimers, and except for DsbCn-PDIb they exhibit new or greatly elevated isomerase as well as chaperone activity. Three-dimensional structure prediction indicates that all the four domain hybrids adopt DsbC-like V-shaped structure with a broad uncharged cleft between the two arms for binding of non-native protein folding intermediates. The results provide strong evidence that dimerization creates chaperone and isomerase activity for monomeric thiol-protein oxidases or reductases, and suggesting a pathway for proteins to acquire new functions and/or higher biological efficiency during evolution.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academi of Sciences, Beijing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.forename: Yi
authors.initials: Y
authors.lastname: Peng
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Hao
authors.forename: Zong-Hao
authors.initials: ZH
authors.lastname: Zeng
authors.forename: Chih-Chen
authors.initials: CC
authors.lastname: Wang
mesh_terms: D001665:Binding Sites; D002942:Circular Dichroism; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000378:metabolism; D019791:Guanidine / Q000737:chemistry; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D019704:Protein Disulfide-Isomerases / Q000737:chemistry; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013879:Thioredoxins / Q000737:chemistry; D013997:Time Factors
chemical_list: D018832:Molecular Chaperones; D013879:Thioredoxins; D019704:Protein Disulfide-Isomerases; D019791:Guanidine