Structural characterization of the MIT domain from human Vps4b
Structural characterization of the MIT domain from human Vps4b
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DOI：
10.1016/j.bbrc.2005.06.110
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发表时间：
2005-08-26
影响因子：
3.1
通讯作者：
Hiroaki, H
中科院分区：
文献类型：
--
作者：
Takasu, H;Jee, JG;Hiroaki, H
微管相互作用和运输（MIT）结构域是一个未知功能的小蛋白模块，在多种功能的蛋白质中是保守的，如Vps 4，分选连接蛋白15（SNX 15）和痉挛蛋白。报道了一种非同义单核苷酸多态性，其导致hVps 4 b中Ile 58-to-Met（I58 M）取代。在这里，我们已经确定了解决方案的结构的MIT域分离的NH 2-末端的人Vps 4 b，AAA-ATP酶参与多泡体的形成。MIT结构域采用“上下”三螺旋束。与其他MIT结构域的序列的比较清楚地表明，参与螺旋间接触的残基是保守的。Ile 58-至-Met取代导致显著的热不稳定性。此外，我们发现螺旋A和C之间的一个浅裂缝，可能作为蛋白质结合位点。我们建议，MIT域作为一个假定的适配器结构域的ESCRT-III复杂的参与内体贩运。(c)2005年爱思唯尔公司All rights reserved.
The microtubule interacting and trafficking (MIT) domain is a small protein module of unknown function that is conserved in proteins of diverse function, such as Vps4, sorting nexin 15 (SNX 15), and spastin. One non-synonymous single nucleotide polymorphism was reported, which results in a Ile58-to-Met (I58M) substitution in hVps4b. Here, we have determined the solution structure of the MIT domain isolated from the NH2-terminus of human Vps4b, an AAA-ATPase involved in multivesicular body formation. The MIT domain adopts an 'up-and-down' three-helix bundle. Comparison with the sequences of other MIT domains clearly shows that the residues involved in inter-helical contacts are well conserved. The Ile58-to-Met substitution resulted a substantial thermal instability. In addition, we found a shallow crevice between helices A and C that may serve as a protein-binding site. We propose that the MIT domain serves as a putative adaptor domain for the ESCRT-III complex involved in endosomal trafficking. (c) 2005 Elsevier Inc. All rights reserved.