6d3r

Thermostablilized dephosphorylated chicken CFTRThermostablilized dephosphorylated chicken CFTR

6d3r, resolution 4.30Å Show:Asymmetric Unit Biological Assembly Structural highlights 6d3r is a 1 chain structure with sequence from Chick. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Gene: CFTR (CHICK) Activity: Channel-conductance-controlling ATPase, with EC number 3.6.3.49 Experimental data: Check Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The cystic fibrosis transmembrane conductance regulator (CFTR) anion channel, crucial to epithelial salt and water homeostasis, and defective due to mutations in its gene in patients with cystic fibrosis, is a unique member of the large family of ATP-binding cassette transport proteins. Regulation of CFTR channel activity is stringently controlled by phosphorylation and nucleotide binding. Structural changes that underlie transitions between active and inactive functional states are not yet fully understood. Indeed the first 3D structures of dephosphorylated, ATP-free and phosphorylated ATP-bound states were only recently reported. Here we have determined the structure of inactive and active states of a thermally stabilized CFTR, the latter with very high channel open probability, confirmed after reconstitution into proteoliposomes. These structures, obtained at nominal resolution of 4.3 and 6.6 A, reveal a unique repositioning of the transmembrane helices and regulatory domain density that provide insights into the structural transition between active and inactive functional states of CFTR. Moreover, we observe an extracellular vestibule that may provide anion access to the pore due to the conformation of transmembrane helices 7 and 8 that differs from the previous orthologue CFTR structures. In conclusion, our work contributes detailed structural information on an active, open state of the CFTR anion channel. Cryo-EM visualization of an active high open probability CFTR anion channel.,Fay JF, Aleksandrov LA, Jensen T, Cui L, Kousouros JN, He L, Aleksandrov AA, Gingerich D, Riordan JR, Chen J Biochemistry. 2018 Oct 3. doi: 10.1021/acs.biochem.8b00763. PMID:30281975 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also ABC transporter 3D structures