Heteromeric amino acid transporters. In search of the molecular bases of transport cycle mechanisms.
Heteromeric amino acid transporters (HATs) are relevant targets for structural studies. On the one hand, HATs are involved in inherited and acquired human pathologies. On the other hand, these molecules are the only known examples of solute transporters composed of two subunits (heavy and light) linked by a disulfide bridge. Unfortunately, structural knowledge of HATs is scarce and limited to the atomic structure of the ectodomain of a heavy subunit (human 4F2hc-ED) and distant prokaryotic homologues of the light subunits that share a LeuT-fold. Recent data on human 4F2hc/LAT2 at nanometer resolution revealed 4F2hc-ED positioned on top of the external loops of the light subunit LAT2. Improved resolution of the structure of HATs, combined with conformational studies, is essential to establish the structural bases for light subunit recognition and to evaluate the functional relevance of heavy and light subunit interactions for the amino acid transport cycle.
Institute for Research in Biomedicine Barcelona (IRB), 08028 Barcelona, Spain The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain Spanish Biomedical Research Center in Rare Diseases (CIBERER), 46010 Valencia, Spain Department of Biochemistry and Molecular Biology, Facultat de Biologia, University of Barcelona, 08028 Barcelona, Spain manuel.palacin@irbbarcelona.org.
Manuel
M
Palacín
Institute for Research in Biomedicine Barcelona (IRB), 08028 Barcelona, Spain The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain Spanish Biomedical Research Center in Rare Diseases (CIBERER), 46010 Valencia, Spain Department of Biochemistry and Molecular Biology, Facultat de Biologia, University of Barcelona, 08028 Barcelona, Spain.
Ekaitz
E
Errasti-Murugarren
Institute for Research in Biomedicine Barcelona (IRB), 08028 Barcelona, Spain The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain Spanish Biomedical Research Center in Rare Diseases (CIBERER), 46010 Valencia, Spain Department of Biochemistry and Molecular Biology, Facultat de Biologia, University of Barcelona, 08028 Barcelona, Spain.
Albert
A
Rosell
D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001419:Bacteria / Q000378:metabolism; D020134:Catalytic Domain; D005796:Genes; D006801:Humans; D011487:Protein Conformation
D026905:Amino Acid Transport Systems
amino acid transporters; heterodimer; heteromeric amino acid transporter (HAT); modelling; structure; transport mechanism