1q3h: Difference between revisions

Revision as of 15:35, 21 February 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 with , and as ligands. 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 Thu Feb 21 14:35:27 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1q3h.gif|left|200px]]<br /><applet load="1q3h" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1q3h.gif|left|200px]]<br /><applet load="1q3h" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1q3h, resolution 2.50&Aring;" />
 '''mouse CFTR NBD1 with AMP.PNP'''<br />
 ==Overview==
-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.
+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 Structure==
-Q3H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with MG, ANP and ACY as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Q3H OCA].
+Q3H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=ANP:'>ANP</scene> and <scene name='pdbligand=ACY:'>ACY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q3H OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Mus musculus]]
 [[Category: Single protein]]
-[[Category: Buchanan, S.G.]]
+[[Category: Buchanan, S G.]]
-[[Category: Burley, S.K.]]
+[[Category: Burley, S K.]]
 [[Category: Conners, K.]]
 [[Category: Dickey, M.]]
@@ Line 20: / Line 20: @@
 [[Category: Fowler, R.]]
 [[Category: Gao, X.]]
-[[Category: Guggino, W.B.]]
+[[Category: Guggino, W B.]]
-[[Category: Hendrickson, W.A.]]
+[[Category: Hendrickson, W A.]]
-[[Category: Lewis, H.A.]]
+[[Category: Lewis, H A.]]
 [[Category: ACY]]
 [[Category: ANP]]
@@ Line 28: / Line 28: @@
 [[Category: abc transporter nucleotide binding domain]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 00:21:16 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:35:27 2008''