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The structure of human 4F2hc ectodomain provides a model for homodimerization and electrostatic interaction with plasma membrane
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname, RIUR. Repositorio Institucional de la Universidad de La Rioja
- Publication Year :
- 2007
- Publisher :
- American Society for Biochemistry and Molecular Biology, 2007.
-
Abstract
- Joana Fort et al.<br />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 Å, respectively. It is composed of a (βα)8 barrel and an antiparallel β8 sandwich related to bacterial α-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 Cys109 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 Cys109 residue located four residues apart from the transmembrane domain, is adjacent to the positive face of the ectodomain. This location of theNterminus and the Cys109-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. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.<br />This work was supported in part by the Spanish Ministry of Science and Education Grant SAF2003-08940, BFU2006-14600, and BIO2005-06753, by the EC Project Grant 502802 EUGINDAT, and by La Marató-TV3
- Subjects :
- Models, Molecular
DNA, Complementary
Fusion Regulatory Protein 1, Heavy Chain
Dimer
Static Electricity
Antiparallel (biochemistry)
Crystallography, X-Ray
Spectrum Analysis, Raman
Transfection
Biochemistry
Models, Biological
Protein Structure, Secondary
chemistry.chemical_compound
Catalytic Domain
Escherichia coli
Humans
Molecular Biology
chemistry.chemical_classification
Cell Membrane
Cell Biology
computer.file_format
Protein Data Bank
Amino acid
Transport protein
Protein Structure, Tertiary
Crystallography
Transmembrane domain
Zinc
Membrane
Cross-Linking Reagents
Ectodomain
chemistry
Biophysics
computer
Dimerization
HeLa Cells
Plasmids
Subjects
Details
- ISSN :
- 20030894
- Database :
- OpenAIRE
- Journal :
- Digital.CSIC. Repositorio Institucional del CSIC, instname, RIUR. Repositorio Institucional de la Universidad de La Rioja
- Accession number :
- edsair.doi.dedup.....fed390835ce67ea1c537f813ee750bbf