6gjq

human NBD1 of CFTR in complex with nanobody T27

spinqualitylabelsall models 6gjq, resolution 2.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6gjq is a 8 chain structure with sequence from Homo sapiens and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.49Å Ligands: ATP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The leading cause of cystic fibrosis (CF) is the deletion of phenylalanine 508 (F508del) in the first nucleotide-binding domain (NBD1) of the cystic fibrosis transmembrane conductance regulator (CFTR). The mutation affects the thermodynamic stability of the domain and the integrity of the interface between NBD1 and the transmembrane domain leading to its clearance by the quality control system. Here, we develop nanobodies targeting NBD1 of human CFTR and demonstrate their ability to stabilize both isolated NBD1 and full-length protein. Crystal structures of NBD1-nanobody complexes provide an atomic description of the epitopes and reveal the molecular basis for stabilization. Furthermore, our data uncover a conformation of CFTR, involving detachment of NBD1 from the transmembrane domain, which contrast with the compact assembly observed in cryo-EM structures. This unexpected interface rearrangement is likely to have major relevance for CF pathogenesis but also for the normal function of CFTR and other ABC proteins. Domain-interface dynamics of CFTR revealed by stabilizing nanobodies.,Sigoillot M, Overtus M, Grodecka M, Scholl D, Garcia-Pino A, Laeremans T, He L, Pardon E, Hildebrandt E, Urbatsch I, Steyaert J, Riordan JR, Govaerts C Nat Commun. 2019 Jun 14;10(1):2636. doi: 10.1038/s41467-019-10714-y. PMID:31201318 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also ABC transporter 3D structures

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