1r0z: Difference between revisions

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New page: left|200px<br /><applet load="1r0z" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r0z, resolution 2.35Å" /> '''Phosphorylated Cysti...
 
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[[Image:1r0z.gif|left|200px]]<br /><applet load="1r0z" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1r0z, resolution 2.35&Aring;" />
'''Phosphorylated Cystic fibrosis transmembrane conductance regulator (CFTR) nucleotide-binding domain one (NBD1) with ATP'''<br />


==Overview==
==Phosphorylated Cystic fibrosis transmembrane conductance regulator (CFTR) nucleotide-binding domain one (NBD1) with ATP==
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.
<StructureSection load='1r0z' size='340' side='right'caption='[[1r0z]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1r0z]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R0Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1R0Z FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1r0z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r0z OCA], [https://pdbe.org/1r0z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r0z RCSB], [https://www.ebi.ac.uk/pdbsum/1r0z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r0z ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CFTR_MOUSE CFTR_MOUSE] 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 (By similarity).
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r0/1r0z_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1r0z ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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==
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<ref>PMID:14685259</ref>
1R0Z 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, ATP 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=1R0Z OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14685259 14685259]
</div>
<div class="pdbe-citations 1r0z" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[ABC transporter 3D structures|ABC transporter 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Single protein]]
[[Category: Buchanan SG]]
[[Category: Buchanan, S.G.]]
[[Category: Burley SK]]
[[Category: Burley, S.K.]]
[[Category: Conners K]]
[[Category: Conners, K.]]
[[Category: Dickey M]]
[[Category: Dickey, M.]]
[[Category: Dorwart M]]
[[Category: Dorwart, M.]]
[[Category: Fowler R]]
[[Category: Fowler, R.]]
[[Category: Gao X]]
[[Category: Gao, X.]]
[[Category: Guggino WB]]
[[Category: Guggino, W.B.]]
[[Category: Hendrickson WA]]
[[Category: Hendrickson, W.A.]]
[[Category: Lewis HA]]
[[Category: Lewis, H.A.]]
[[Category: ACY]]
[[Category: ATP]]
[[Category: MG]]
[[Category: abc transporter nucleotide binding domain]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 01:10:44 2007''

Latest revision as of 07:17, 30 October 2024

Phosphorylated Cystic fibrosis transmembrane conductance regulator (CFTR) nucleotide-binding domain one (NBD1) with ATP

1r0z, resolution 2.35Å

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