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	Structural basis of human ABCC4 recognition of cAMP and ligand recognition flexibility.
Journal, issue, pages	Cell Biosci, Vol. 15, Issue 1, Page 39, Year 2025
Publish date	Mar 27, 2025
Authors	Xuepeng Wen / Kaixue Si / Dantong Zhu / Anqi Zhang / Changyou Guo / Minghui Li / Weiming Tian /
PubMed Abstract	BACKGROUND: ABCC4 (ATP-binding cassette sub-family C member 4) is a transporter protein that is primarily localized to the plasma membrane, and its efflux activity is associated with the progression ...BACKGROUND: ABCC4 (ATP-binding cassette sub-family C member 4) is a transporter protein that is primarily localized to the plasma membrane, and its efflux activity is associated with the progression of various cancers and the development of drug resistance. Cyclic adenosine monophosphate (cAMP) is an important biomolecule that is considered a transport substrate of ABCC4. However, there is currently no direct structural understanding of how ABCC4 binds cAMP, and the mechanisms by which it recognizes a diverse range of substrate ligands remain poorly understood. Some studies have indicated that, under physiological conditions, cAMP does not significantly stimulate the ATPase activity of ABCC4, making the commonly used ATPase activity assays for ABC proteins unsuitable for studying cAMP. RESULTS: Here, we successfully resolved the cryo-electron microscopy (cryo-EM) structure of the human ABCC4-cAMP (hABCC4-cAMP) complex, revealing how hABCC4 binds to cAMP and identifying the key residues involved. This structure was compared with two other hABCC4 complex structures we obtained (Methotrexate and Prostaglandin E) and with previously published structures. We discovered some new structural insights into how hABCC4 binds ligands. On the basis of the structural information obtained, we confirmed the feasibility of using 8-[Fluo]-cAMP in a transport assay to detect cAMP translocation and found that some challenges remain to be addressed. CONCLUSIONS: These results suggest that hABCC4 can bind cAMP and exhibits varying degrees of flexibility when binding with different substrates, including cAMP. These findings expand our understanding of the structural biology of ABCC4.
External links	Cell Biosci / PubMed:40148998 / PubMed Central
Methods	EM (single particle)
Resolution	2.99 - 3.29 Å
Structure data	62531 9krk EMDB-62531, PDB-9krk: Cryo-EM structure of human ABCC4 (Apo state) Method: EM (single particle) / Resolution: 3.29 Å 62532 9krl EMDB-62532, PDB-9krl: Cryo-EM structure of human ABCC4 (cAMP-bound) Method: EM (single particle) / Resolution: 2.99 Å 62533 9krm EMDB-62533, PDB-9krm: Cryo-EM structure of human ABCC4 (MTX-bound) Method: EM (single particle) / Resolution: 3.0 Å 62534 9krn EMDB-62534, PDB-9krn: Cryo-EM structure of human ABCC4 (PGE2-bound) Method: EM (single particle) / Resolution: 3.14 Å
Chemicals	ChemComp-CMP: ADENOSINE-3',5'-CYCLIC-MONOPHOSPHATE ChemComp-MTX: METHOTREXATE / chemotherapyYM ChemComp-P2E: (Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxo-cyclopentyl]hept-5-enoic acid / medicationYM
Source	homo sapiens (human)
Keywords	TRANSPORT PROTEIN / ABC-type transporter activity / ATP hydrolysis activity / ATPase-coupled transmembrane transporter activity / ATP binding / Transport protein.