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	Transport mechanism of human bilirubin transporter ABCC2 tuned by the inter-module regulatory domain.
Journal, issue, pages	Nat Commun, Vol. 15, Issue 1, Page 1061, Year 2024
Publish date	Feb 5, 2024
Authors	Yao-Xu Mao / Zhi-Peng Chen / Liang Wang / Jie Wang / Cong-Zhao Zhou / Wen-Tao Hou / Yuxing Chen /
PubMed Abstract	Bilirubin is mainly generated from the breakdown of heme when red blood cells reach the end of their lifespan. Accumulation of bilirubin in human body usually leads to various disorders, including ...Bilirubin is mainly generated from the breakdown of heme when red blood cells reach the end of their lifespan. Accumulation of bilirubin in human body usually leads to various disorders, including jaundice and liver disease. Bilirubin is conjugated in hepatocytes and excreted to bile duct via the ATP-binding cassette transporter ABCC2, dysfunction of which would lead to Dubin-Johnson syndrome. Here we determine the structures of ABCC2 in the apo, substrate-bound and ATP/ADP-bound forms using the cryo-electron microscopy, exhibiting a full transporter with a regulatory (R) domain inserted between the two half modules. Combined with substrate-stimulated ATPase and transport activity assays, structural analysis enables us to figure out transport cycle of ABCC2 with the R domain adopting various conformations. At the rest state, the R domain binding to the translocation cavity functions as an affinity filter that allows the substrates of high affinity to be transported in priority. Upon substrate binding, the R domain is expelled from the cavity and docks to the lateral of transmembrane domain following ATP hydrolysis. Our findings provide structural insights into a transport mechanism of ABC transporters finely tuned by the R domain.
External links	Nat Commun / PubMed:38316776 / PubMed Central
Methods	EM (single particle)
Resolution	3.32 - 4.17 Å
Structure data	36691 8jx7 EMDB-36691, PDB-8jx7: Cryo-EM structure of human ABC transporter ABCC2 Method: EM (single particle) / Resolution: 3.6 Å 36709 8jxq EMDB-36709, PDB-8jxq: Cryo-EM structure of bilirubin ditaurate (BDT) bound human ABC transporter ABCC2 Method: EM (single particle) / Resolution: 3.32 Å 36713 8jxu EMDB-36713, PDB-8jxu: Cryo-EM structure of human ABC transporter ABCC2 under active turnover condition Method: EM (single particle) / Resolution: 3.55 Å 36719 8jy4 EMDB-36719, PDB-8jy4: Cryo-EM structure of human ABC transporter ABCC2 in apo' state Method: EM (single particle) / Resolution: 3.58 Å 36720 8jy5 EMDB-36720, PDB-8jy5: Cryo-EM structure of human ABC transporter ABCC2 in apo" state Method: EM (single particle) / Resolution: 4.17 Å
Chemicals	ChemComp-CLR: CHOLESTEROL / Cholesterol ChemComp-FEI: 2-[3-[5-[(E)-(4-ethenyl-3-methyl-5-oxidanylidene-pyrrol-2-ylidene)methyl]-2-[[5-[(3-ethenyl-4-methyl-5-oxidanylidene-pyrrol-2-ylidene)methyl]-4-methyl-3-[3-oxidanylidene-3-(2-sulfoethylamino)propyl]-1H-pyrrol-2-yl]methyl]-4-methyl-1H-pyrrol-3-yl]propanoylamino]ethanesulfonic acid ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying moleculeYM / Adenosine diphosphate ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying moleculeYM / Adenosine triphosphate ChemComp-MG: Unknown entry
Source	homo sapiens (human)
Keywords	TRANSPORT PROTEIN / ATP-dependent transporter / conjugated organic anions transporter / ATP hydrolyzes / bilirubin / ABC transporter