6yup
From Proteopedia
Heterotetrameric structure of the rBAT-b(0,+)AT1 complex
Structural highlights
DiseaseSLC31_HUMAN Cystinuria type A;2p21 microdeletion syndrome;Atypical hypotonia-cystinuria syndrome;Hypotonia-cystinuria syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Hypotonia-cystinuria syndrome is a contiguous gene syndrome caused by a homozygous deletion on chromosome 2p21 that disrupts the gene represented in this entry and PREPL (PubMed:16385448, PubMed:21686663). A homozygous 77.4-kb deletion that disrupts the gene represented in this entry, PREPL, and CAMKMT, causes atypical hypotonia-cystinuria syndrome, characterized by mild to moderate mental retardation and respiratory chain complex IV deficiency (PubMed:21686663).[1] [2] FunctionSLC31_HUMAN Involved in the high-affinity, sodium-independent transport of cystine and neutral and dibasic amino acids (system B(0,+)-like activity). May function as an activator of SLC7A9 and be involved in the high-affinity reabsorption of cystine in the kidney tubule.[3] [4] [5] [6] Publication Abstract from PubMedHeteromeric amino acid transporters (HATs) comprise a group of membrane proteins that belong to the solute carrier (SLC) superfamily. They are formed by two different protein components: a light chain subunit from an SLC7 family member and a heavy chain subunit from the SLC3 family. The light chain constitutes the transport subunit whereas the heavy chain mediates trafficking to the plasma membrane and maturation of the functional complex. Mutation, malfunction, and dysregulation of HATs are associated with a wide range of pathologies or represent the direct cause of inherited and acquired disorders. Here we report the cryogenic electron microscopy structure of the neutral and basic amino acid transport complex (b([0,+])AT1-rBAT) which reveals a heterotetrameric protein assembly composed of two heavy and light chain subunits, respectively. The previously uncharacterized interaction between two HAT units is mediated via dimerization of the heavy chain subunits and does not include participation of the light chain subunits. The b((0,+))AT1 transporter adopts a LeuT fold and is captured in an inward-facing conformation. We identify an amino-acid-binding pocket that is formed by transmembrane helices 1, 6, and 10 and conserved among SLC7 transporters. Structural basis for amino acid exchange by a human heteromeric amino acid transporter.,Wu D, Grund TN, Welsch S, Mills DJ, Michel M, Safarian S, Michel H Proc Natl Acad Sci U S A. 2020 Sep 1;117(35):21281-21287. doi:, 10.1073/pnas.2008111117. Epub 2020 Aug 17. PMID:32817565[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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