Pathway leading to correctly folded beta-tubulin.
We describe the complete beta-tubulin folding pathway. Folding intermediates produced via ATP-dependent interaction with cytosolic chaperonin undergo a sequence of interactions with four proteins (cofactors A, D, E, and C). The postchaperonin steps in the reaction cascade do not depend on ATP or GTP hydrolysis, although GTP plays a structural role in tubulin folding. Cofactors A and D function by capturing and stabilizing beta-tubulin in a quasi-native conformation. Cofactor E binds to the cofactor D-beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. Sequence analysis identifies yeast homologs of cofactors D (cin1) and E (pac2), characterized by mutations that affect microtubule function.
Tian
G
G
Department of Biochemistry, New York University Medical Center, New York 10016, USA.
Huang
Y
Y
Rommelaere
H
H
Vandekerckhove
J
J
Ampe
C
C
Cowan
N J
NJ
D000818:Animals; D002417:Cattle; D002457:Cell Extracts / Q000737:chemistry; D018833:Chaperonins / Q000502:physiology; D010450:Endopeptidases; D008297:Male; D008969:Molecular Sequence Data; D017510:Protein Folding; D011506:Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D011817:Rabbits; D012680:Sensitivity and Specificity; D017386:Sequence Homology, Amino Acid; D014404:Tubulin / Q000032:analysis / Q000737:chemistry*
D002457:Cell Extracts; D011506:Proteins; D014404:Tubulin; D010450:Endopeptidases; D018833:Chaperonins