1q3h: Difference between revisions
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'''mouse CFTR NBD1 with AMP.PNP''' | '''mouse CFTR NBD1 with AMP.PNP''' | ||
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[[Category: Hendrickson, W A.]] | [[Category: Hendrickson, W A.]] | ||
[[Category: Lewis, H A.]] | [[Category: Lewis, H A.]] | ||
[[Category: | [[Category: Abc transporter nucleotide binding domain]] | ||
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Revision as of 05:49, 3 May 2008
mouse CFTR NBD1 with AMP.PNP
OverviewOverview
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.
About this StructureAbout this Structure
1Q3H is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
Structure of nucleotide-binding domain 1 of the cystic fibrosis transmembrane conductance regulator., Lewis HA, Buchanan SG, Burley SK, Conners K, Dickey M, Dorwart M, Fowler R, Gao X, Guggino WB, Hendrickson WA, Hunt JF, Kearins MC, Lorimer D, Maloney PC, Post KW, Rajashankar KR, Rutter ME, Sauder JM, Shriver S, Thibodeau PH, Thomas PJ, Zhang M, Zhao X, Emtage S, EMBO J. 2004 Jan 28;23(2):282-93. Epub 2003 Dec 18. PMID:14685259 Page seeded by OCA on Sat May 3 05:49:14 2008