Structure of the small GTPase Rab27b shows an unexpected swapped dimer
Structure of the small GTPase Rab27b shows an unexpected swapped dimer
复制标题
DOI：
10.1107/s0907444907019725
复制
发表时间：
2007-07-01
影响因子：
2.2
通讯作者：
Wakatsuki, Soichi
中科院分区：
文献类型：
--
作者：
Chavas, Leonard M. G.;Torii, Seiji;Wakatsuki, Soichi
小GTP酶的Rab家族成员通过以核苷酸依赖性方式募集其特异性效应物来调节细胞内的膜运输。Rab 27亚家族由Rab 27 a和Rab 27 b组成，它们共享70%的序列同一性。Rab 27 a和Rab 27 b通过与大量的效应蛋白如亲黑素和颗粒蛋白相互作用，调节分泌性溶酶体的胞吐作用。在这里，小鼠Rab 27 b与GDP复合物的晶体结构已在三种不同的晶格中确定。令人惊讶的是，Rab 27 b-GDP以开放构象存在，具有突出的开关和开关间区域，其通过晶体中的结构域交换通过二聚化而稳定。相反，小角X射线散射测量显示Rab 27 b在溶液中的扩展单体形式。在晶体中观察到Rab 27 b-GDP的二聚体形成将抑制高度柔性的开关区域。Rab 27 b的这种非典型结构及其在效应器相互作用中的合理影响可能的生物学意义进行了讨论。
Members of the Rab family of small GTPases regulate membrane traffic within the cell by recruiting their specific effectors in a nucleotide-dependent manner. The Rab27 subfamily consists of Rab27a and Rab27b, which share 70% sequence identity. By interacting with a large set of effector proteins such as melanophilin and granuphilin, both Rab27a and Rab27b regulate the exocytosis of secretory lysosomes. Here, the crystal structures of mouse Rab27b in complex with GDP have been determined in three distinct crystal lattices. Surprisingly, Rab27b-GDP exists in an open conformation with protruding switch and interswitch regions, which are stabilized through dimerization by means of domain-swapping in the crystals. In contrast, small-angle X-ray scattering measurements showed an extended monomer form of Rab27b in solution. The observed dimer formation of Rab27b-GDP in the crystals would restrain the highly flexible switch regions. Possible biological implications of this atypical structure of Rab27b and its plausible influence in effector interaction are discussed.