Computation and Functional Studies Provide a Model for the Structure of the Zinc Transporter hZIP4

被引:55
作者
Antala, Sagar [2 ]
Ovchinnikov, Sergey [3 ,4 ,5 ]
Kamisetty, Hetunandan [3 ,4 ]
Baker, David [3 ,4 ]
Dempski, Robert E. [1 ,2 ]
机构
[1] Worcester Polytech Inst, Dept Chem & Biochem, Worcester, MA 01609 USA
[2] Worcester Polytech Inst, Dept Chem & Biochem, Worcester, MA 01609 USA
[3] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA
[4] Univ Washington, Dept Biochem, Seattle, WA 98195 USA
[5] Univ Washington, Mol & Cellular Biol Program, Seattle, WA 98195 USA
基金
美国国家卫生研究院;
关键词
MAJOR FACILITATOR SUPERFAMILY; MIX-AND-MATCH; ACRODERMATITIS-ENTEROPATHICA; ESCHERICHIA-COLI; STRUCTURE PREDICTION; PROTEIN STRUCTURES; MFS TRANSPORTERS; ZNT TRANSPORTERS; BINDING; SEQUENCE;
D O I
10.1074/jbc.M114.617613
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
Members of the Zrt and Irt protein (ZIP) family are a central participant in transition metal homeostasis as they function to increase the cytosolic concentration of zinc and/or iron. However, the lack of a crystal structure hinders elucidation of the molecular mechanism of ZIP proteins. Here, we employed GREMLIN, a co-evolution-based contact prediction approach in conjunction with the Rosetta structure prediction program to construct a structural model of the human (h) ZIP4 transporter. The predicted contact data are best fit by modeling hZIP4 as a dimer. Mutagenesis of residues that comprise a central putative hZIP4 transmembrane transition metal coordination site in the structural model alter the kinetics and specificity of hZIP4. Comparison of the hZIP4 dimer model to all known membrane protein structures identifies the 12-transmembrane monomeric Piriformospora indica phosphate transporter (PiPT), a member of the major facilitator superfamily (MFS), as a likely structural homolog.
引用
收藏
页码:17796 / 17805
页数:10
相关论文
共 46 条
[1]   The Human ZIP4 Transporter Has Two Distinct Binding Affinities and Mediates Transport of Multiple Transition Metals [J].
Antala, Sagar ;
Dempski, Robert E. .
BIOCHEMISTRY, 2012, 51 (05) :963-973
[2]   The large intracellular loop of hZIP4 is an intrinsically disordered zinc binding domain [J].
Bafaro, Elizabeth M. ;
Antala, Sagar ;
Tuong-Vi Nguyen ;
Dzul, Stephen P. ;
Doyon, Brian ;
Stemmler, Timothy L. ;
Dempski, Robert E. .
METALLOMICS, 2015, 7 (09) :1319-1330
[3]   Toward high-resolution prediction and design of transmembrane helical protein structures [J].
Barth, P. ;
Schonbrun, J. ;
Baker, D. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (40) :15682-15687
[4]   MESSA: MEta-Server for protein Sequence Analysis [J].
Cong, Qian ;
Grishin, Nick V. .
BMC BIOLOGY, 2012, 10
[5]   Inward-facing conformation of the zinc transporter YiiP revealed by cryoelectron microscopy [J].
Coudray, Nicolas ;
Valvo, Salvatore ;
Hu, Minghui ;
Lasala, Ralph ;
Kim, Changki ;
Vink, Martin ;
Zhou, Ming ;
Provasi, Davide ;
Filizola, Marta ;
Tao, Juoehi ;
Fang, Jia ;
Penczek, Pawel A. ;
Ubarretxena-Belandia, Iban ;
Stokes, David L. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (06) :2140-2145
[6]   The Cation Selectivity of the ZIP Transporters [J].
Dempski, Robert E. .
METAL TRANSPORTERS, 2012, 69 :221-245
[7]   Modeling Symmetric Macromolecular Structures in Rosetta3 [J].
DiMaio, Frank ;
Leaver-Fay, Andrew ;
Bradley, Phil ;
Baker, David ;
Andre, Ingemar .
PLOS ONE, 2011, 6 (06)
[8]   Functional Significance of E2 State Stabilization by Specific α/β-Subunit Interactions of Na,K- and H,K-ATPase [J].
Duerr, Katharina L. ;
Tavraz, Neslihan N. ;
Dempski, Robert E. ;
Bamberg, Ernst ;
Friedrich, Thomas .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (06) :3842-3854
[9]   The acrodermatitis enteropathica gene ZIP4 encodes a tissue-specific, zinc-regulated zinc transporter in mice [J].
Dufner-Beattie, J ;
Wang, FD ;
Kuo, YM ;
Gitschier, J ;
Eide, D ;
Andrews, GK .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (35) :33474-33481
[10]   Structure, function, and regulation of a subfamily of mouse zinc transporter genes [J].
Dufner-Beattie, J ;
Langmade, SJ ;
Wang, FD ;
Eide, D ;
Andrews, GK .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (50) :50142-50150