| Structural highlights
6lid is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| Gene: | SLC3A1, RBAT (HUMAN), SLC7A9, BAT1 (HUMAN) |
| 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] [BAT1_HUMAN] Cystinuria type B. The disease is caused by mutations affecting the gene represented in this entry.
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] [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.[7] [8] [9]
Publication Abstract from PubMed
Heteromeric amino acid transporters (HATs) catalyze the transmembrane movement of amino acids, comprising two subunits, a heavy chain and a light chain, linked by a disulfide bridge. The b(0,+)AT (SLC7A9) is a representative light chain of HATs, forming heterodimer with rBAT, a heavy chain which mediates the membrane trafficking of b(0,+)AT. The b(0,+)AT-rBAT complex is an obligatory exchanger, which mediates the influx of cystine and cationic amino acids and the efflux of neutral amino acids in kidney and small intestine. Here, we report the cryo-EM structure of the human b(0,+)AT-rBAT complex alone and in complex with arginine substrate at resolution of 2.7 and 2.3 A, respectively. The overall structure of b(0,+)AT-rBAT exists as a dimer of heterodimer consistent with the previous study. A ligand molecule is bound to the substrate binding pocket, near which an occluded pocket is identified, to which we found that it is important for substrate transport.
Cryo-EM structure of the human heteromeric amino acid transporter b(0,+)AT-rBAT.,Yan R, Li Y, Shi Y, Zhou J, Lei J, Huang J, Zhou Q Sci Adv. 2020 Apr 15;6(16):eaay6379. doi: 10.1126/sciadv.aay6379. eCollection, 2020 Apr. PMID:32494597[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Yan R, Li Y, Shi Y, Zhou J, Lei J, Huang J, Zhou Q. Cryo-EM structure of the human heteromeric amino acid transporter b(0,+)AT-rBAT. Sci Adv. 2020 Apr 15;6(16):eaay6379. doi: 10.1126/sciadv.aay6379. eCollection, 2020 Apr. PMID:32494597 doi:http://dx.doi.org/10.1126/sciadv.aay6379
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