Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Recognition of cyclic dinucleotides and folates by human SLC19A1.
Journal, issue, pages	Nature, Vol. 612, Issue 7938, Page 170-176, Year 2022
Publish date	Oct 20, 2022
Authors	Qixiang Zhang / Xuyuan Zhang / Yalan Zhu / Panpan Sun / Liwei Zhang / Junxiao Ma / Yong Zhang / Lingan Zeng / Xiaohua Nie / Yina Gao / Zhaolong Li / Songqing Liu / Jizhong Lou / Ang Gao / Liguo Zhang / Pu Gao /
PubMed Abstract	Cyclic dinucleotides (CDNs) are ubiquitous signalling molecules in all domains of life. Mammalian cells produce one CDN, 2'3'-cGAMP, through cyclic GMP-AMP synthase after detecting cytosolic DNA ...Cyclic dinucleotides (CDNs) are ubiquitous signalling molecules in all domains of life. Mammalian cells produce one CDN, 2'3'-cGAMP, through cyclic GMP-AMP synthase after detecting cytosolic DNA signals. 2'3'-cGAMP, as well as bacterial and synthetic CDN analogues, can act as second messengers to activate stimulator of interferon genes (STING) and elicit broad downstream responses. Extracellular CDNs must traverse the cell membrane to activate STING, a process that is dependent on the solute carrier SLC19A1. Moreover, SLC19A1 represents the major transporter for folate nutrients and antifolate therapeutics, thereby placing SLC19A1 as a key factor in multiple physiological and pathological processes. How SLC19A1 recognizes and transports CDNs, folate and antifolate is unclear. Here we report cryo-electron microscopy structures of human SLC19A1 (hSLC19A1) in a substrate-free state and in complexes with multiple CDNs from different sources, a predominant natural folate and a new-generation antifolate drug. The structural and mutagenesis results demonstrate that hSLC19A1 uses unique yet divergent mechanisms to recognize CDN- and folate-type substrates. Two CDN molecules bind within the hSLC19A1 cavity as a compact dual-molecule unit, whereas folate and antifolate bind as a monomer and occupy a distinct pocket of the cavity. Moreover, the structures enable accurate mapping and potential mechanistic interpretation of hSLC19A1 with loss-of-activity and disease-related mutations. Our research provides a framework for understanding the mechanism of SLC19-family transporters and is a foundation for the development of potential therapeutics.
External links	Nature / PubMed:36265513
Methods	EM (single particle)
Resolution	3.0 - 3.4 Å
Structure data	33386 7xpz EMDB-33386, PDB-7xpz: Structure of Apo-hSLC19A1 Method: EM (single particle) / Resolution: 3.4 Å 33387 7xq0 EMDB-33387, PDB-7xq0: Structure of hSLC19A1+3'3'-CDA Method: EM (single particle) / Resolution: 3.0 Å 33388 7xq1 EMDB-33388, PDB-7xq1: Structure of hSLC19A1+2'3'-CDAS Method: EM (single particle) / Resolution: 3.4 Å 33389 7xq2 EMDB-33389, PDB-7xq2: Structure of hSLC19A1+2'3'-cGAMP Method: EM (single particle) / Resolution: 3.3 Å 34176 8goe EMDB-34176, PDB-8goe: Structure of hSLC19A1+5-MTHF Method: EM (single particle) / Resolution: 3.0 Å 34177 8gof EMDB-34177, PDB-8gof: Structure of hSLC19A1+PMX Method: EM (single particle) / Resolution: 3.0 Å
Chemicals	ChemComp-2BA: (2R,3R,3aS,5R,7aR,9R,10R,10aS,12R,14aR)-2,9-bis(6-amino-9H-purin-9-yl)octahydro-2H,7H-difuro[3,2-d:3',2'-j][1,3,7,9,2,8 ChemComp-GJF: (1~{R},3~{S},6~{R},8~{R},9~{R},10~{S},12~{S},15~{R},17~{R},18~{R})-8,17-bis(6-aminopurin-9-yl)-3,12-bis(oxidanylidene)-3,12-bis(sulfanyl)-2,4,7,11,13,16-hexaoxa-3$l^{5},12$l^{5}-diphosphatricyclo[13.2.1.0^{6,10}]octadecane-9,18-diol ChemComp-1SY: cGAMP ChemComp-THH: N-[4-({[(6S)-2-AMINO-4-HYDROXY-5-METHYL-5,6,7,8-TETRAHYDROPTERIDIN-6-YL]METHYL}AMINO)BENZOYL]-L-GLUTAMIC ACID ChemComp-LYA: 2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-PENTANEDIOIC ACID / medication, chemotherapy*YM
Source	homo sapiens (human)
Keywords	MEMBRANE PROTEIN / SLC19A1 / hSLC19A1+3'3'-CDA complex / SLC19A1+2'3'-CDAS complex / hSLC19A1+2'3'-cGAMP complex / hSLC19A1+5-MTHF complex / hSLC19A1+PMX complex