期刊
CURRENT BIOLOGY
卷 22, 期 12, 页码 1066-1074出版社
CELL PRESS
DOI: 10.1016/j.cub.2012.05.012
关键词
-
资金
- National Institutes of Health [RO1NS047715, RO1EB006745, DP2OD006466]
- National Science Foundation (NSF) [EF1038697]
- Stanford University School of Medicine
- NSF [OCI-1053575, TG-MCB110056]
Background: Microtubules are built from linear polymers of alpha-beta tubulin dimers (protofilaments) that form a tubular quinary structure. Microtubules assembled from purified tubulin in vitro contain between 10 and 16 protofilaments; however, such structural polymorphisms are not found in cells. This discrepancy implies that factors other than tubulin constrain microtubule protofilament number, but the nature of these constraints is unknown. Results: Here, we show that acetylation of MEC-12 alpha-tubulin constrains protofilament number in C. elegans touch receptor neurons (TRNs). Whereas the sensory dendrite of wildtype TRNs is packed with a cross-linked bundle of long, 15-protofilament microtubules, mec-17;atat-2 mutants lacking alpha-tubulin acetyltransferase activity have short microtubules, rampant lattice defects, and variable protofilament number both between and within microtubules. All-atom molecular dynamics simulations suggest a model in which acetylation of lysine 40 promotes the formation of interprotofilament salt bridges, stabilizing lateral interactions between protofilaments and constraining quinary structure to produce stable, structurally uniform microtubules in vivo. Conclusions: Acetylation of alpha-tubulin is an essential constraint on protofilament number in vivo. We propose a structural model in which this posttranslational modification promotes the formation of lateral salt bridges that fine-tune the association between adjacent protofilaments and enable the formation of uniform microtubule populations in vivo.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据