Structural Biology of Human Dynamin

Dynamin是一种由五个结构域组成的大型延伸蛋白质。我们已经测定了人Dynamin 1衍生的最小GTPase-GED(即“GTPase效应域”)融合蛋白的2.0埃分辨率晶体结构。该融合蛋白在模拟GDP-氟化铝的过渡态存在下二聚。该结构揭示了Dynamin的催化机制，并解释了组装刺激的GTP水解是如何通过G结构域二聚实现的。尤其耐人寻味的是在活性部位发现了一个钠离子，这表明Dynamin使用阳离子来补偿过渡状态中正在形成的负离子，并为之前无法牵涉到更常见的精氨酸手指提供了理论基础。这种融合结构域的结构使我们能够为动力蛋白催化的膜分裂中二聚体的作用提供一个模型。最近，我们用基态GTP类似物确定了GTPase-GED融合的结构。结构显示分子的一部分发生了令人惊讶的重新定向。我们认为，运动可能在向膜传递构象信息方面具有重要意义。 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容地中海医院。88,339-350。

Dynamin is a large, extended protein consisting of five domains. We have determined the 2.0 Angstrom resolution crystal structure of a human dynamin 1-derived minimal GTPase-GED (for "GTPase effector domain") fusion protein. This fusion protein dimerizes in the presence of the transition state mimic GDP-aluminum fluoride. The structure reveals dynamin's catalytic machinery and explains how assembly-stimulated GTP hydrolysis is achieved through G domain dimerization. Particularly intriguing was the identification of a sodium ion in the active site, suggesting that dynamin uses a cation to compensate for the developing negative in the transition state and providing a rationale for the inability to previously implicate a more-usual arginine finger. The structure of this fusion domain allows us to provide a model for the role of dimerization during dynamin-catalyzed membrane fission. Recently, we have determined the structure of the GTPase-GED fusion with a ground state GTP analog. The structure showed a surprising reorientation of a part of the molecule. We believe that movement may have significance in transmitting conformational information toward the membrane. Durieux, A.C., Prudhon, B., Guicheney, P., and Bitoun, M. (2010) J. Mol. Med. 88, 339-350.