The structure of human 4F2hc ectodomain provides a model for homodimerization and electrostatic interaction with plasma membrane

被引:94
作者
Fort, Joana
de la Ballina, Laura R.
Burghardt, Hans E.
Ferrer-Costa, Carles
Turnay, Javier
Ferrer-Orta, Cristina
Uson, Isabel
Zorzano, Antonio
Fernandez-Recio, Juan
Orozco, Modesto
Lizarbe, Maria Antonia
Fita, Ignacio
Palacin, Manuel [1 ]
机构
[1] Univ Barcelona, Ctr Invest Biomed Red Enfermedades Raras, Inst Res Biomed, Fac Biol,Dept Biochem & Mol Biol, E-08028 Barcelona, Spain
[2] Univ Complutense, Fac Ciencias Quim, Dept Bioquim & Biol Mol 1, E-28040 Madrid, Spain
[3] Inst Mol Biol, ICREA, E-08028 Barcelona, Spain
[4] Supercomp Ctr, E-08028 Barcelona, Spain
关键词
D O I
10.1074/jbc.M704524200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:31444 / 31452
页数:9
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