Structure-function relationships of heterodimeric amino acid transporters.
Heterodimeric amino acid transporters mediate the transfer of amino acids between organs and between different cell types. Members of this particular family of amino acid transporters are constituted by a heavy chain and an associated light chain. The heavy chain is a type II membrane protein with an intracellular amino terminus, a single transmembrane helix, and a large extracellular domain. The light chain, in contrast, is a typical helix-bundle protein with 12 putative transmembrane helices. Two different heavy chains, designated 4F2hc and rbAT, and seven different light chains have been identified to date. Deletion studies indicate that the extracellular domain of the heavy chain has two subdomains. The carboxy-terminal tip of 4F2hc is critical for recognition of certain light chains, whereas the carboxy-terminal tip of rbAT is involved in substrate transport. Sequence alignments suggest that the major part of the extracellular domain forms an alpha/beta domain similar to bacterial alpha-amylases. A structural model of the rbAT extracellular domain is presented that is in agreement with experimental observations from several mutations and that aligns well with the alpha-amylase domain.
Bröer
Stefan
S
School of Biochemistry and Molecular Biology, Australian National University, Canberra, ACT. stefan.broeer@anu.edu.au
Wagner
Carsten A
CA
D026905:Amino Acid Transport Systems / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D026923:Amino Acid Transport Systems, Basic; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D003555:Cystinuria / Q000235:genetics; D019281:Dimerization; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D027261:Fusion Regulatory Protein-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D017384:Sequence Deletion; D013329:Structure-Activity Relationship
D026905:Amino Acid Transport Systems; D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D027282:Fusion Regulatory Protein 1, Heavy Chain; D027261:Fusion Regulatory Protein-1; D008562:Membrane Glycoproteins; D021122:Protein Subunits; C499489:SLC7A9 protein, human