Cofactor A Is a Molecular Chaperone Required for -Tubulin Folding: Functional and Structural Characterization
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- 作者：Ronald Melki ; Heidi Rommelaere ; Robin Leguy ; Joë ; l Vandekerckhove ; and Christophe Ampe
- 刊名：Biochemistry
- 出版年：1996
- 出版时间：August 13, 1996
- 年：1996
- 卷：35
- 期：32
- 页码：10422 - 10435
- 全文大小：538K
- 年卷期：v.35,no.32(August 13, 1996)
- ISSN：1520-4995
文摘
Actin and tubulin polypeptide chains acquire their nativeconformation in the presence of thechaperonin containing TCP-1 (CCT) and, in the case of 
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-tubulin additional protein cofactors.We recently identified one of these cofactors, termed cofactor A,that is required for the proper foldingof the -tubulin chain [Gao et al. (1994) J.Cell. Biol. 125, 989-996]. Weshow here that cofactor A,a monomeric protein that has no measurable affinity for nucleotides, isa highly conserved protein amongvertebrates. Its NH2-terminal region is essential forthe structural integrity of the protein and consequentlyfor its activity. We demonstrate that cofactor A does not interactwith CCT nor does it affect the intrinsicATPase activity of CCT, alone or in the presence of different targetproteins. Thus, unlike GroES, cofactorA does not modulate or coordinate ATP hydrolysis. It does not actas a nucleotide exchange factor or acatalyst in tubulin folding. Rather, we demonstrate that cofactorA participates in the tubulin foldingprocess by interacting with a folding intermediate of -tubulin thatis released from CCT. Our dataimply that cofactor A is a chaperone involved in tubulinfolding.
- and-tubulin additional protein cofactors.We recently identified one of these cofactors, termed cofactor A,that is required for the proper foldingof the -tubulin chain [Gao et al. (1994) J.Cell. Biol. 125, 989-996]. Weshow here that cofactor A,a monomeric protein that has no measurable affinity for nucleotides, isa highly conserved protein amongvertebrates. Its NH2-terminal region is essential forthe structural integrity of the protein and consequentlyfor its activity. We demonstrate that cofactor A does not interactwith CCT nor does it affect the intrinsicATPase activity of CCT, alone or in the presence of different targetproteins. Thus, unlike GroES, cofactorA does not modulate or coordinate ATP hydrolysis. It does not actas a nucleotide exchange factor or acatalyst in tubulin folding. Rather, we demonstrate that cofactorA participates in the tubulin foldingprocess by interacting with a folding intermediate of -tubulin thatis released from CCT. Our dataimply that cofactor A is a chaperone involved in tubulinfolding.