1R10

Cystic fibrosis transmembrane conductance regulator (CFTR) nucleotide-binding domain one (NBD1) with ATP, I4122 space group

Summary for 1R10

• Entry DOI: 10.2210/pdb1r10/pdb
• Related: 1R0W 1R0X 1R0Y 1R0Z
• Descriptor: Cystic fibrosis transmembrane conductance regulator, MAGNESIUM ION, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: abc transporter nucleotide binding domain, transport protein
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 2
• Total formula weight: 65439.78

Authors

Lewis, H.A.,Buchanan, S.G.,Burley, S.K.,Conners, K.,Dickey, M.,Dorwart, M.,Fowler, R.,Gao, X.,Guggino, W.B.,Hendrickson, W.A. (deposition date: 2003-09-23, release date: 2003-12-09, Last modification date: 2024-02-14)

Primary citation

Lewis, H.A.,Buchanan, S.G.,Burley, S.K.,Conners, K.,Dickey, M.,Dorwart, M.,Fowler, R.,Gao, X.,Guggino, W.B.,Hendrickson, W.A.,Hunt, J.F.,Kearins, M.C.,Lorimer, D.,Maloney, P.C.,Post, K.W.,Rajashankar, K.R.,Rutter, M.E.,Sauder, J.M.,Shriver, S.,Thibodeau, P.H.,Thomas, P.J.,Zhang, M.,Zhao, X.,Emtage, S.
Structure of nucleotide-binding domain 1 of the cystic fibrosis transmembrane conductance regulator.
Embo J., 23:282-293, 2004

PubMed Abstract: Cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-binding cassette (ABC) transporter that functions as a chloride channel. Nucleotide-binding domain 1 (NBD1), one of two ABC domains in CFTR, also contains sites for the predominant CF-causing mutation and, potentially, for regulatory phosphorylation. We have determined crystal structures for mouse NBD1 in unliganded, ADP- and ATP-bound states, with and without phosphorylation. This NBD1 differs from typical ABC domains in having added regulatory segments, a foreshortened subdomain interconnection, and an unusual nucleotide conformation. Moreover, isolated NBD1 has undetectable ATPase activity and its structure is essentially the same independent of ligand state. Phe508, which is commonly deleted in CF, is exposed at a putative NBD1-transmembrane interface. Our results are consistent with a CFTR mechanism, whereby channel gating occurs through ATP binding in an NBD1-NBD2 nucleotide sandwich that forms upon displacement of NBD1 regulatory segments.

PubMed: 14685259
DOI: 10.1038/sj.emboj.7600040

Experimental method

X-RAY DIFFRACTION (3 Å)