6yv1

From Proteopedia

Structure of human b(0,+)AT1

Structural highlights

6yv1 is a 1 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 3.4Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

BAT1_HUMAN Cystinuria type B. The disease is caused by mutations affecting the gene represented in this entry.

Function

BAT1_HUMAN Involved in the high-affinity, sodium-independent transport of cystine and neutral and dibasic amino acids (system b(0,+)-like activity). Thought to be responsible for the high-affinity reabsorption of cystine in the kidney tubule.^[1] ^[2] ^[3]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Feliubadalo L, Font M, Purroy J, Rousaud F, Estivill X, Nunes V, Golomb E, Centola M, Aksentijevich I, Kreiss Y, Goldman B, Pras M, Kastner DL, Pras E, Gasparini P, Bisceglia L, Beccia E, Gallucci M, de Sanctis L, Ponzone A, Rizzoni GF, Zelante L, Bassi MT, George AL Jr, Manzoni M, De Grandi A, Riboni M, Endsley JK, Ballabio A, Borsani G, Reig N, Fernandez E, Estevez R, Pineda M, Torrents D, Camps M, Lloberas J, Zorzano A, Palacin M. Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (bo,+AT) of rBAT. Nat Genet. 1999 Sep;23(1):52-7. doi: 10.1038/12652. PMID:10471498 doi:http://dx.doi.org/10.1038/12652
↑ Pfeiffer R, Loffing J, Rossier G, Bauch C, Meier C, Eggermann T, Loffing-Cueni D, Kuhn LC, Verrey F. Luminal heterodimeric amino acid transporter defective in cystinuria. Mol Biol Cell. 1999 Dec;10(12):4135-47. doi: 10.1091/mbc.10.12.4135. PMID:10588648 doi:http://dx.doi.org/10.1091/mbc.10.12.4135
↑ Shigeta Y, Kanai Y, Chairoungdua A, Ahmed N, Sakamoto S, Matsuo H, Kim DK, Fujimura M, Anzai N, Mizoguchi K, Ueda T, Akakura K, Ichikawa T, Ito H, Endou H. A novel missense mutation of SLC7A9 frequent in Japanese cystinuria cases affecting the C-terminus of the transporter. Kidney Int. 2006 Apr;69(7):1198-206. doi: 10.1038/sj.ki.5000241. PMID:16609684 doi:http://dx.doi.org/10.1038/sj.ki.5000241
↑ 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