The structure of the human 4F2hc-LAT1 heteromeric amino acid transporter
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摘要
<正>Amino acids are biologically important molecules that serve as energy source, building blocks of proteins, precursors for metabolites and signaling compounds in all living cells.Transport of proteinogenic amino acids and related substances across biological membranes is mediated by membrane embedded proteins:the amino acid transporters. These membrane proteins belong to different solute carrier (SLC)families (http://slc.bioparadigms.org) and transfer amino acids in and out between compartments inside cells, between different cells and between organs. Amino acid transporters have diverse important physiological functions and their absence, overexpression and malfunction can lead to human diseases.
引文
Cheng,Y.,Grigorieff,N.,Penczek,P.A.,and Walz,T.(2015).A primer to single-particle cryo-electron microscopy.Cell 161,438-449.
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Jeckelmann,J.-M.,and Fotiadis,D.(2019).Volta phase plate cryo-EMstructure of the human heterodimeric amino acid transporter 4F2hcLAT2.IJMS 20,931.
Meury,M.,Costa,M.,Harder,D.,Stauffer,M.,Jeckelmann,J.-M.,Brühlmann,B.,Rosell,A.,Ilgü,H.,Kovar,K.,Palacín,M.,et al.(2014).Detergent-induced stabilization and improved 3D map of the human heteromeric amino acid transporter 4F2hc-LAT2.PLoS ONE 9,e109882.
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Rosell,A.,Meury,M.,álvarez-Marimon,E.,Costa,M.,Pérez-Cano,L.,Zorzano,A.,Fernández-Recio,J.,Palacín,M.,and Fotiadis,D.(2014).Structural bases for the interaction and stabilization of the human amino acid transporter LAT2 with its ancillary protein 4F2hc.Proc Natl Acad Sci USA 111,2966-2971.
Scalise,M.,Galluccio,M.,Console,L.,Pochini,L.,and Indiveri,C.(2018).The human SLC7A5(LAT1):The intriguing histidine/large neutral amino acid transporter and its relevance to human health.Front Chem 6,243.
T?rlungeanu,D.C.,Deliu,E.,Dotter,C.P.,Kara,M.,Janiesch,P.C.,Scalise,M.,Galluccio,M.,Tesulov,M.,Morelli,E.,Sonmez,F.M.,et al.(2016).Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder.Cell 167,1481-1494.e18.
Yan,R.,Zhao,X.,Lei,J.,and Zhou,Q.(2019).Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex.Nature 568,127-130.
Zur,A.A.,Chien,H.C.,Augustyn,E.,Flint,A.,Heeren,N.,Finke,K.,Hernandez,C.,Hansen,L.,Miller,S.,Lin,L.,et al.(2016).LAT1activity of carboxylic acid bioisosteres:Evaluation of hydroxamic acids as substrates.BioOrg Medicinal Chem Lett 26,5000-5006.
Chien,H.C.,Colas,C.,Finke,K.,Springer,S.,Stoner,L.,Zur,A.A.,Venteicher,B.,Campbell,J.,Hall,C.,Flint,A.,et al.(2018).Reevaluating the substrate specificity of the L-type amino acid transporter(LAT1).J Med Chem 61,7358-7373.
Fort,J.,de la Ballina,L.R.,Burghardt,H.E.,Ferrer-Costa,C.,Turnay,J.,Ferrer-Orta,C.,Usón,I.,Zorzano,A.,Fernández-Recio,J.,Orozco,M.,et al.(2007).The structure of human 4F2hc ectodomain provides a model for homodimerization and electrostatic interaction with plasma membrane.J Biol Chem 282,31444-31452.
Fotiadis,D.,Kanai,Y.,and Palacín,M.(2013).The SLC3 and SLC7families of amino acid transporters.Mol Aspects Med 34,139-158.
Geier,E.G.,Schlessinger,A.,Fan,H.,Gable,J.E.,Irwin,J.J.,Sali,A.,and Giacomini,K.M.(2013).Structure-based ligand discovery for the largeneutral amino acid transporter 1,LAT-1.Proc Natl Acad Sci USA 110,5480-5485.
Ilgü,H.,Jeckelmann,J.-M.,Colas,C.,Ucurum,Z.,Schlessinger,A.,and Fotiadis,D.(2018).Effects of mutations and ligands on the thermostability of the L-arginine/agmatine antiporter AdiC and deduced insights into ligand-binding of human L-type amino acid transporters.IJMS 19,918.
Ilgü,H.,Jeckelmann,J.-M.,Gapsys,V.,Ucurum,Z.,de Groot,B.L.,and Fotiadis,D.(2016).Insights into the molecular basis for substrate binding and specificity of the wild-type L-arginine/agmatine antiporter AdiC.Proc Natl Acad Sci USA 113,10358-10363.
Jeckelmann,J.-M.,and Fotiadis,D.(2019).Volta phase plate cryo-EMstructure of the human heterodimeric amino acid transporter 4F2hcLAT2.IJMS 20,931.
Meury,M.,Costa,M.,Harder,D.,Stauffer,M.,Jeckelmann,J.-M.,Brühlmann,B.,Rosell,A.,Ilgü,H.,Kovar,K.,Palacín,M.,et al.(2014).Detergent-induced stabilization and improved 3D map of the human heteromeric amino acid transporter 4F2hc-LAT2.PLoS ONE 9,e109882.
Nii,T.,Segawa,H.,Taketani,Y.,Tani,Y.,Ohkido,M.,Kishida,S.,Ito,M.,Endou,H.,Kanai,Y.,Takeda,E.,et al.(2001).Molecular events involved in up-regulating human Na+-independent neutral amino acid transporter LAT1 during T-cell activation.Biochem J 358,693-704.
Rosell,A.,Meury,M.,álvarez-Marimon,E.,Costa,M.,Pérez-Cano,L.,Zorzano,A.,Fernández-Recio,J.,Palacín,M.,and Fotiadis,D.(2014).Structural bases for the interaction and stabilization of the human amino acid transporter LAT2 with its ancillary protein 4F2hc.Proc Natl Acad Sci USA 111,2966-2971.
Scalise,M.,Galluccio,M.,Console,L.,Pochini,L.,and Indiveri,C.(2018).The human SLC7A5(LAT1):The intriguing histidine/large neutral amino acid transporter and its relevance to human health.Front Chem 6,243.
T?rlungeanu,D.C.,Deliu,E.,Dotter,C.P.,Kara,M.,Janiesch,P.C.,Scalise,M.,Galluccio,M.,Tesulov,M.,Morelli,E.,Sonmez,F.M.,et al.(2016).Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder.Cell 167,1481-1494.e18.
Yan,R.,Zhao,X.,Lei,J.,and Zhou,Q.(2019).Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex.Nature 568,127-130.
Zur,A.A.,Chien,H.C.,Augustyn,E.,Flint,A.,Heeren,N.,Finke,K.,Hernandez,C.,Hansen,L.,Miller,S.,Lin,L.,et al.(2016).LAT1activity of carboxylic acid bioisosteres:Evaluation of hydroxamic acids as substrates.BioOrg Medicinal Chem Lett 26,5000-5006.