The structure of human 4F2hc ectodomain provides a model for homodimerization and electrostatic interaction with plasma membrane
The structure of human 4F2hc ectodomain provides a model for homodimerization and electrostatic interaction with plasma membrane
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DOI：
10.1074/jbc.m704524200
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发表时间：
2007-10-26
影响因子：
4.8
通讯作者：
Palacin, Manuel
中科院分区：
文献类型：
--
作者：
Fort, Joana;de la Ballina, Laura R.;Palacin, Manuel
4F 2 hc（CD 98 hc）是一种多功能的II型膜糖蛋白，参与氨基酸转运和细胞融合、粘附和转化。人4F 2 hc的胞外域的结构已经分别在2.1和2.8埃下使用单斜晶型（蛋白质数据库代码2DH 2）和正交晶型（蛋白质数据库代码2DH 3）解析。它由与细菌α-糖苷酶相关的（β α）（8）桶和反平行β（8）夹心组成，尽管缺乏关键催化残基和因此的催化活性。2DH 3是在界面处具有Zn 2+配位的二聚体。在几种细胞类型中表达的人4F 2 hc导致细胞表面和Cys（109）二硫键连接的同源二聚体，其具有晶体二聚体的主要结构特征，如交联实验所证明的。4F 2 hc在表面没有明显的疏水斑块。单聚体和同二聚体具有极化的带电表面。解析结构的N末端，包括位于离跨膜结构域四个残基的Cys（109）残基的位置，邻近胞外域的正表面。N末端和Cys（109）-间插二硫键的位置施加了空间限制，足以支持4F 2 hc胞外域与膜磷脂的静电相互作用的模型。这些结果提供了异聚氨基酸转运蛋白的第一个晶体结构，并表明4F 2 hc胞外域与质膜的动态相互作用。
4F2hc ( CD98hc) is a multifunctional type II membrane glycoprotein involved in amino acid transport and cell fusion, adhesion, and transformation. The structure of the ectodomain of human 4F2hc has been solved using monoclinic ( Protein Data Bank code 2DH2) and orthorhombic ( Protein Data Bank code 2DH3) crystal forms at 2.1 and 2.8 angstrom, respectively. It is composed of a (beta alpha)(8) barrel and an antiparallel beta(8) sandwich related to bacterial alpha- glycosidases, although lacking key catalytic residues and consequently catalytic activity. 2DH3 is a dimer with Zn2+ coordination at the interface. Human 4F2hc expressed in several cell types resulted in cell surface and Cys(109) disulfide bridge- linked homodimers with major architectural features of the crystal dimer, as demonstrated by cross- linking experiments. 4F2hc has no significant hydrophobic patches at the surface. Monomer and homodimer have a polarized charged surface. The N terminus of the solved structure, including the position of Cys(109) residue located four residues apart from the transmembrane domain, is adjacent to the positive face of the ectodomain. This location of the N terminus and the Cys(109)-intervening disulfide bridge imposes space restrictions sufficient to support a model for electrostatic interaction of the 4F2hc ectodomain with membrane phospholipids. These results provide the first crystal structure of heteromeric amino acid transporters and suggest a dynamic interaction of the 4F2hc ectodomain with the plasma membrane.