2pze

Minimal human CFTR first nucleotide binding domain as a head-to-tail dimer

spinqualitylabelsall models 2pze, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2pze is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ATP, MG Related: 1xmi, 1xmj, 2bb0, 2bbs, 2bbt, 1r0z, 1r10, 2ixe, 1l2t, 1q12, 1xef, 2hyd, 2pzf, 2pzg Gene: CFTR, ABCC7 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [CFTR_HUMAN] Defects in CFTR are the cause of cystic fibrosis (CF) [MIM:219700]; also known as mucoviscidosis. CF is the most common genetic disease in the Caucasian population, with a prevalence of about 1 in 2'000 live births. Inheritance is autosomal recessive. CF is a common generalized disorder of exocrine gland function which impairs clearance of secretions in a variety of organs. It is characterized by the triad of chronic bronchopulmonary disease (with recurrent respiratory infections), pancreatic insufficiency (which leads to malabsorption and growth retardation) and elevated sweat electrolytes. Defects in CFTR are the cause of congenital bilateral absence of the vas deferens (CBAVD) [MIM:277180]. CBAVD is an important cause of sterility in men and could represent an incomplete form of cystic fibrosis, as the majority of men suffering from cystic fibrosis lack the vas deferens. [:] Function [CFTR_HUMAN] Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter. Can inhibit the chloride channel activity of ANO1. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Upon removal of the regulatory insert (RI), the first nucleotide binding domain (NBD1) of human cystic fibrosis transmembrane conductance regulator (CFTR) can be heterologously expressed and purified in a form that remains stable without solubilizing mutations, stabilizing agents or the regulatory extension (RE). This protein, NBD1 387-646(Delta405-436), crystallizes as a homodimer with a head-to-tail association equivalent to the active conformation observed for NBDs from symmetric ATP transporters. The 1.7-A resolution X-ray structure shows how ATP occupies the signature LSGGQ half-site in CFTR NBD1. The DeltaF508 version of this protein also crystallizes as a homodimer and differs from the wild-type structure only in the vicinity of the disease-causing F508 deletion. A slightly longer construct crystallizes as a monomer. Comparisons of the homodimer structure with this and previously published monomeric structures show that the main effect of ATP binding at the signature site is to order the residues immediately preceding the signature sequence, residues 542-547, in a conformation compatible with nucleotide binding. These residues likely interact with a transmembrane domain intracellular loop in the full-length CFTR channel. The experiments described here show that removing the RI from NBD1 converts it into a well-behaved protein amenable to biophysical studies yielding deeper insights into CFTR function. Structures of a minimal human CFTR first nucleotide-binding domain as a monomer, head-to-tail homodimer, and pathogenic mutant.,Atwell S, Brouillette CG, Conners K, Emtage S, Gheyi T, Guggino WB, Hendle J, Hunt JF, Lewis HA, Lu F, Protasevich II, Rodgers LA, Romero R, Wasserman SR, Weber PC, Wetmore D, Zhang FF, Zhao X Protein Eng Des Sel. 2010 May;23(5):375-84. Epub 2010 Feb 11. PMID:20150177 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also ABC transporter Ion channels

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