1tc0: Difference between revisions

Revision as of 16:11, 21 February 2008

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

OverviewOverview

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 StructureAbout 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.

ReferenceReference

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

Page seeded by OCA on Thu Feb 21 15:11:58 2008

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

OCA

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-[[Image:1tc0.gif|left|200px]]<br /><applet load="1tc0" size="450" color="white" frame="true" align="right" spinBox="true"
+[[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;" />
 '''Ligand Induced Conformational Shifts in the N-terminal Domain of GRP94, Open Conformation Complexed with the physiological partner ATP'''<br />
 ==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.
+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==
-TC0 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].
+TC0 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==
@@ Line 13: / Line 13: @@
 [[Category: Canis lupus familiaris]]
 [[Category: Single protein]]
-[[Category: Dollins, D.E.]]
+[[Category: Dollins, D E.]]
-[[Category: Gewirth, D.T.]]
+[[Category: Gewirth, D T.]]
-[[Category: Immormino, R.M.]]
+[[Category: Immormino, R M.]]
-[[Category: Shaffer, P.L.]]
+[[Category: Shaffer, P L.]]
-[[Category: Soldano, K.L.]]
+[[Category: Soldano, K L.]]
-[[Category: Walker, M.A.]]
+[[Category: Walker, M A.]]
 [[Category: ATP]]
 [[Category: MG]]
@@ Line 29: / Line 29: @@
 [[Category: hsp90]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:08:43 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:11:58 2008''