1ypw
From Proteopedia
(New page: 200px<br /><applet load="1ypw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ypw, resolution 3.50Å" /> '''Structure of p97/VCP...) |
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| - | [[Image:1ypw.gif|left|200px]]<br /><applet load="1ypw" size=" | + | [[Image:1ypw.gif|left|200px]]<br /><applet load="1ypw" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ypw, resolution 3.50Å" /> | caption="1ypw, resolution 3.50Å" /> | ||
'''Structure of p97/VCP in Complex in ADP/AMP-PNP'''<br /> | '''Structure of p97/VCP in Complex in ADP/AMP-PNP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The AAA (ATPases associated with a variety of cellular activities) family | + | The AAA (ATPases associated with a variety of cellular activities) family of proteins bind, hydrolyze, and release ATP to effect conformational changes, assembly, or disassembly upon their binding partners and substrate molecules. One of the members of this family, the hexameric p97/valosin-containing protein p97/VCP, is essential for the dislocation of misfolded membrane proteins from the endoplasmic reticulum. Here, we observe large motions and dynamic changes of p97/VCP as it proceeds through the ATP hydrolysis cycle. The analysis is based on crystal structures of four representative ATP hydrolysis states: APO, AMP-PNP, hydrolysis transition state ADP x AlF3, and ADP bound. Two of the structures presented herein, ADP and AMP-PNP bound, are new structures, and the ADP x AlF3 structure was re-refined to higher resolution. The largest motions occur at two stages during the hydrolysis cycle: after, but not upon, nucleotide binding and then following nucleotide release. The motions occur primarily in the D2 domain, the D1 alpha-helical domain, and the N-terminal domain, relative to the relatively stationary and invariant D1alpha/beta domain. In addition to the motions, we observed a transition from a rigid state to a flexible state upon loss of the gamma-phosphate group, and a further increase in flexibility within the D2 domains upon nucleotide release. The domains within each protomer of the hexameric p97/VCP deviate from strict 6-fold symmetry, with the more flexible ADP state exhibiting greater asymmetry compared to the relatively rigid ADP x AlF3 state, suggesting a mechanism of action in which hydrolysis and conformational changes move about the hexamer in a processive fashion. |
==About this Structure== | ==About this Structure== | ||
| - | 1YPW 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 ADP and ANP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1YPW 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=ADP:'>ADP</scene> and <scene name='pdbligand=ANP:'>ANP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YPW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Brunger, A | + | [[Category: Brunger, A T.]] |
[[Category: Delabarre, B.]] | [[Category: Delabarre, B.]] | ||
[[Category: ADP]] | [[Category: ADP]] | ||
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[[Category: p97/vcp]] | [[Category: p97/vcp]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:07:54 2008'' |
Revision as of 14:07, 21 February 2008
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Structure of p97/VCP in Complex in ADP/AMP-PNP
Overview
The AAA (ATPases associated with a variety of cellular activities) family of proteins bind, hydrolyze, and release ATP to effect conformational changes, assembly, or disassembly upon their binding partners and substrate molecules. One of the members of this family, the hexameric p97/valosin-containing protein p97/VCP, is essential for the dislocation of misfolded membrane proteins from the endoplasmic reticulum. Here, we observe large motions and dynamic changes of p97/VCP as it proceeds through the ATP hydrolysis cycle. The analysis is based on crystal structures of four representative ATP hydrolysis states: APO, AMP-PNP, hydrolysis transition state ADP x AlF3, and ADP bound. Two of the structures presented herein, ADP and AMP-PNP bound, are new structures, and the ADP x AlF3 structure was re-refined to higher resolution. The largest motions occur at two stages during the hydrolysis cycle: after, but not upon, nucleotide binding and then following nucleotide release. The motions occur primarily in the D2 domain, the D1 alpha-helical domain, and the N-terminal domain, relative to the relatively stationary and invariant D1alpha/beta domain. In addition to the motions, we observed a transition from a rigid state to a flexible state upon loss of the gamma-phosphate group, and a further increase in flexibility within the D2 domains upon nucleotide release. The domains within each protomer of the hexameric p97/VCP deviate from strict 6-fold symmetry, with the more flexible ADP state exhibiting greater asymmetry compared to the relatively rigid ADP x AlF3 state, suggesting a mechanism of action in which hydrolysis and conformational changes move about the hexamer in a processive fashion.
About this Structure
1YPW is a Single protein structure of sequence from Mus musculus with and as ligands. Full crystallographic information is available from OCA.
Reference
Nucleotide dependent motion and mechanism of action of p97/VCP., DeLaBarre B, Brunger AT, J Mol Biol. 2005 Mar 25;347(2):437-52. PMID:15740751
Page seeded by OCA on Thu Feb 21 16:07:54 2008
Categories: Mus musculus | Single protein | Brunger, A T. | Delabarre, B. | ADP | ANP | Aaa | Cdc48 | Erad | P97/vcp
