6yup

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Heterotetrameric structure of the rBAT-b(0,+)AT1 complex

Structural highlights

6yup is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 2.9Å
Ligands:CA, NAG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SLC31_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]

Function

SLC31_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 PubMed

Heteromeric 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.

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Citations
2 reviews cite this structure
Heteromeric Amino Acid Transporters in Brain: from Physiology to Pathology.
Errasti-Murugarren et al. (2022)
1 more
11 other articles
No citations found

References

  1. ↑ Jaeken J, Martens K, Francois I, Eyskens F, Lecointre C, Derua R, Meulemans S, Slootstra JW, Waelkens E, de Zegher F, Creemers JW, Matthijs G. Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome. Am J Hum Genet. 2006 Jan;78(1):38-51. Epub 2005 Nov 23. PMID:16385448 doi:http://dx.doi.org/S0002-9297(07)60804-0
  2. ↑ Chabrol B, Martens K, Meulemans S, Cano A, Jaeken J, Matthijs G, Creemers JW. Deletion of C2orf34, PREPL and SLC3A1 causes atypical hypotonia-cystinuria syndrome. BMJ Case Rep. 2009;2009. pii: bcr08.2008.0719. doi: 10.1136/bcr.08.2008.0719., Epub 2009 Feb 2. PMID:21686663 doi:http://dx.doi.org/10.1136/bcr.08.2008.0719
  3. ↑ Mizoguchi K, Cha SH, Chairoungdua A, Kim DK, Shigeta Y, Matsuo H, Fukushima J, Awa Y, Akakura K, Goya T, Ito H, Endou H, Kanai Y. Human cystinuria-related transporter: localization and functional characterization. Kidney Int. 2001 May;59(5):1821-33. PMID:11318953 doi:http://dx.doi.org/kid686
  4. ↑ Bertran J, Werner A, Chillaron J, Nunes V, Biber J, Testar X, Zorzano A, Estivill X, Murer H, Palacin M. Expression cloning of a human renal cDNA that induces high affinity transport of L-cystine shared with dibasic amino acids in Xenopus oocytes. J Biol Chem. 1993 Jul 15;268(20):14842-9. PMID:7686906
  5. ↑ Lee WS, Wells RG, Sabbag RV, Mohandas TK, Hediger MA. Cloning and chromosomal localization of a human kidney cDNA involved in cystine, dibasic, and neutral amino acid transport. J Clin Invest. 1993 May;91(5):1959-63. doi: 10.1172/JCI116415. PMID:8486766 doi:http://dx.doi.org/10.1172/JCI116415
  6. ↑ Miyamoto K, Segawa H, Tatsumi S, Katai K, Yamamoto H, Taketani Y, Haga H, Morita K, Takeda E. Effects of truncation of the COOH-terminal region of a Na+-independent neutral and basic amino acid transporter on amino acid transport in Xenopus oocytes. J Biol Chem. 1996 Jul 12;271(28):16758-63. PMID:8663184
  7. ↑ Wu D, Grund TN, Welsch S, Mills DJ, Michel M, Safarian S, Michel H. Structural basis for amino acid exchange by a human heteromeric amino acid transporter. Proc Natl Acad Sci U S A. 2020 Sep 1;117(35):21281-21287. PMID:32817565 doi:10.1073/pnas.2008111117

Contents


PDB ID 6yup

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