Misra S, Beach B M, Hurley J H
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0580, USA.
Biochemistry. 2000 Sep 19;39(37):11282-90. doi: 10.1021/bi0013546.
VHS domains are found at the N-termini of select proteins involved in intracellular membrane trafficking. We have determined the crystal structure of the VHS domain of the human Tom1 (target of myb 1) protein to 1.5 A resolution. The domain consists of eight helices arranged in a superhelix. The surface of the domain has two main features: (1) a basic patch on one side due to several conserved positively charged residues on helix 3 and (2) a negatively charged ridge on the opposite side, formed by residues on helix 2. We compare our structure to the recently obtained structure of tandem VHS-FYVE domains from Hrs [Mao, Y., Nickitenko, A., Duan, X., Lloyd, T. E., Wu, M. N., Bellen, H., and Quiocho, F. A. (2000) Cell 100, 447-456]. Key features of the interaction surface between the FYVE and VHS domains of Hrs, involving helices 2 and 4 of the VHS domain, are conserved in the VHS domain of Tom1, even though Tom1 does not have a FYVE domain. We also compare the structures of the VHS domains of Tom1 and Hrs to the recently obtained structure of the ENTH domain of epsin-1 [Hyman, J., Chen, H., Di Fiore, P. P., De Camilli, P., and Brünger, A. T. (2000) J. Cell Biol. 149, 537-546]. Comparison of the two VHS domains and the ENTH domain reveals a conserved surface, composed of helices 2 and 4, that is utilized for protein-protein interactions. In addition, VHS domain-containing proteins are often localized to membranes. We suggest that the conserved positively charged surface of helix 3 in VHS and ENTH domains plays a role in membrane binding.
VHS结构域存在于参与细胞内膜运输的特定蛋白质的N端。我们已确定人类Tom1（myb 1的靶点）蛋白的VHS结构域的晶体结构，分辨率达到1.5埃。该结构域由八个螺旋排列成一个超螺旋。该结构域的表面有两个主要特征：（1）一侧有一个碱性斑块，这是由于螺旋3上几个保守的带正电荷残基造成的；（2）另一侧有一个带负电荷的脊，由螺旋2上的残基形成。我们将我们的结构与最近获得的来自Hrs的串联VHS - FYVE结构域的结构进行比较[毛，Y.，尼基滕科，A.，段，X.，劳埃德，T. E.，吴，M. N.，贝伦，H.，和基奥乔，F. A.（2000年）《细胞》100卷，447 - 456页]。Hrs的FYVE和VHS结构域之间相互作用表面的关键特征，涉及VHS结构域的螺旋2和4，在Tom1的VHS结构域中是保守的，尽管Tom1没有FYVE结构域。我们还将Tom1和Hrs的VHS结构域的结构与最近获得的epsin - 1的ENTH结构域的结构进行比较[海曼，J.，陈，H.，迪菲奥雷，P. P.，德卡米利，P.，和布伦格，A. T.（2000年）《细胞生物学杂志》149卷，537 - 546页]。对这两个VHS结构域和ENTH结构域的比较揭示了一个由螺旋2和4组成的保守表面，该表面用于蛋白质 - 蛋白质相互作用。此外，含有VHS结构域 的蛋白质通常定位于膜上。我们认为VHS和ENTH结构域中螺旋3保守的带正电荷表面在膜结合中起作用。
