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1tc0

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(New page: 200px<br /><applet load="1tc0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tc0, resolution 2.20&Aring;" /> '''Ligand Induced Confo...)
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[[Image:1tc0.gif|left|200px]]<br /><applet load="1tc0" size="450" color="white" frame="true" align="right" spinBox="true"
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[[Image:1tc0.gif|left|200px]]<br /><applet load="1tc0" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1tc0, resolution 2.20&Aring;" />
caption="1tc0, resolution 2.20&Aring;" />
'''Ligand Induced Conformational Shifts in the N-terminal Domain of GRP94, Open Conformation Complexed with the physiological partner ATP'''<br />
'''Ligand Induced Conformational Shifts in the N-terminal Domain of GRP94, Open Conformation Complexed with the physiological partner ATP'''<br />
==Overview==
==Overview==
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GRP94 is the endoplasmic reticulum paralog of cytoplasmic Hsp90. Models of, Hsp90 action posit an ATP-dependent conformational switch in the, N-terminal ligand regulatory domain of the chaperone. However, crystal, structures of the isolated N-domain of Hsp90 in complex with a variety of, ligands have yet to demonstrate such a conformational change. We have, determined the structure of the N-domain of GRP94 in complex with ATP, ADP, and AMP. Compared with the N-ethylcarboxamidoadenosine and, radicicol-bound forms, these structures reveal a large conformational, rearrangement in the protein. The nucleotide-bound form exposes new, surfaces that interact to form a biochemically plausible dimer that is, reminiscent of those seen in structures of MutL and DNA gyrase. Weak ATP, binding and a conformational change in response to ligand identity are, distinctive mechanistic features of GRP94 and suggest a model for how, GRP94 functions in the absence of co-chaperones and ATP hydrolysis.
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GRP94 is the endoplasmic reticulum paralog of cytoplasmic Hsp90. Models of Hsp90 action posit an ATP-dependent conformational switch in the N-terminal ligand regulatory domain of the chaperone. However, crystal structures of the isolated N-domain of Hsp90 in complex with a variety of ligands have yet to demonstrate such a conformational change. We have determined the structure of the N-domain of GRP94 in complex with ATP, ADP, and AMP. Compared with the N-ethylcarboxamidoadenosine and radicicol-bound forms, these structures reveal a large conformational rearrangement in the protein. The nucleotide-bound form exposes new surfaces that interact to form a biochemically plausible dimer that is reminiscent of those seen in structures of MutL and DNA gyrase. Weak ATP binding and a conformational change in response to ligand identity are distinctive mechanistic features of GRP94 and suggest a model for how GRP94 functions in the absence of co-chaperones and ATP hydrolysis.
==About this Structure==
==About this Structure==
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1TC0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Canis_lupus_familiaris Canis lupus familiaris] with MG, ATP and PG4 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TC0 OCA].
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1TC0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Canis_lupus_familiaris Canis lupus familiaris] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=ATP:'>ATP</scene> and <scene name='pdbligand=PG4:'>PG4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TC0 OCA].
==Reference==
==Reference==
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[[Category: Canis lupus familiaris]]
[[Category: Canis lupus familiaris]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Dollins, D.E.]]
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[[Category: Dollins, D E.]]
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[[Category: Gewirth, D.T.]]
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[[Category: Gewirth, D T.]]
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[[Category: Immormino, R.M.]]
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[[Category: Immormino, R M.]]
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[[Category: Shaffer, P.L.]]
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[[Category: Shaffer, P L.]]
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[[Category: Soldano, K.L.]]
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[[Category: Soldano, K L.]]
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[[Category: Walker, M.A.]]
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[[Category: Walker, M A.]]
[[Category: ATP]]
[[Category: ATP]]
[[Category: MG]]
[[Category: MG]]
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[[Category: hsp90]]
[[Category: hsp90]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:08:43 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:11:58 2008''

Revision as of 13:11, 21 February 2008


1tc0, resolution 2.20Å

Drag the structure with the mouse to rotate

Ligand Induced Conformational Shifts in the N-terminal Domain of GRP94, Open Conformation Complexed with the physiological partner ATP

Overview

GRP94 is the endoplasmic reticulum paralog of cytoplasmic Hsp90. Models of Hsp90 action posit an ATP-dependent conformational switch in the N-terminal ligand regulatory domain of the chaperone. However, crystal structures of the isolated N-domain of Hsp90 in complex with a variety of ligands have yet to demonstrate such a conformational change. We have determined the structure of the N-domain of GRP94 in complex with ATP, ADP, and AMP. Compared with the N-ethylcarboxamidoadenosine and radicicol-bound forms, these structures reveal a large conformational rearrangement in the protein. The nucleotide-bound form exposes new surfaces that interact to form a biochemically plausible dimer that is reminiscent of those seen in structures of MutL and DNA gyrase. Weak ATP binding and a conformational change in response to ligand identity are distinctive mechanistic features of GRP94 and suggest a model for how GRP94 functions in the absence of co-chaperones and ATP hydrolysis.

About this Structure

1TC0 is a Single protein structure of sequence from Canis lupus familiaris with , and as ligands. Full crystallographic information is available from OCA.

Reference

Ligand-induced conformational shift in the N-terminal domain of GRP94, an Hsp90 chaperone., Immormino RM, Dollins DE, Shaffer PL, Soldano KL, Walker MA, Gewirth DT, J Biol Chem. 2004 Oct 29;279(44):46162-71. Epub 2004 Aug 2. PMID:15292259

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