3d6t

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: '''Unreleased structure''' The entry 3d6t is ON HOLD Authors: Deng, J., Lewis, P.A., Greggio, E., Sluch, E., Beilina, A., Cookson, M.R. Description: Structure of the ROC domain from th...)
Line 1: Line 1:
-
'''Unreleased structure'''
+
[[Image:3d6t.jpg|left|200px]]
-
The entry 3d6t is ON HOLD
+
<!--
 +
The line below this paragraph, containing "STRUCTURE_3d6t", creates the "Structure Box" on the page.
 +
You may change the PDB parameter (which sets the PDB file loaded into the applet)
 +
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
 +
or leave the SCENE parameter empty for the default display.
 +
-->
 +
{{STRUCTURE_3d6t| PDB=3d6t | SCENE= }}
-
Authors: Deng, J., Lewis, P.A., Greggio, E., Sluch, E., Beilina, A., Cookson, M.R.
+
'''Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase'''
-
Description: Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase
 
 +
==Overview==
 +
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of Parkinson's disease (PD). LRRK2 contains a Ras of complex proteins (ROC) domain that may act as a GTPase to regulate its protein kinase activity. The structure of ROC and the mechanism(s) by which it regulates kinase activity are not known. Here, we report the crystal structure of the LRRK2 ROC domain in complex with GDP-Mg(2+) at 2.0-A resolution. The structure displays a dimeric fold generated by extensive domain-swapping, resulting in a pair of active sites constructed with essential functional groups contributed from both monomers. Two PD-associated pathogenic residues, R1441 and I1371, are located at the interface of two monomers and provide exquisite interactions to stabilize the ROC dimer. The structure demonstrates that loss of stabilizing forces in the ROC dimer is likely related to decreased GTPase activity resulting from mutations at these sites. Our data suggest that the ROC domain may regulate LRRK2 kinase activity as a dimer, possibly via the C-terminal of ROC (COR) domain as a molecular hinge. The structure of the LRRK2 ROC domain also represents a signature from a previously undescribed class of GTPases from complex proteins and results may provide a unique molecular target for therapeutics in PD.
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 11 09:37:42 2008''
+
==About this Structure==
 +
3D6T is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D6T OCA].
 +
 
 +
==Reference==
 +
Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase., Deng J, Lewis PA, Greggio E, Sluch E, Beilina A, Cookson MR, Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1499-504. Epub 2008 Jan 29. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18230735 18230735]
 +
[[Category: Homo sapiens]]
 +
[[Category: Non-specific serine/threonine protein kinase]]
 +
[[Category: Single protein]]
 +
[[Category: Deng, J.]]
 +
[[Category: Atp-binding]]
 +
[[Category: Coiled coil]]
 +
[[Category: Cytoplasm]]
 +
[[Category: Disease mutation]]
 +
[[Category: Gtp-binding]]
 +
[[Category: Gtpase]]
 +
[[Category: Gtpase activation]]
 +
[[Category: Kinase]]
 +
[[Category: Leucine-rich repeat]]
 +
[[Category: Lrrk2]]
 +
[[Category: Membrane]]
 +
[[Category: Nucleotide-binding]]
 +
[[Category: Parkinson disease]]
 +
[[Category: Parkinson's disease]]
 +
[[Category: Polymorphism]]
 +
[[Category: Roc]]
 +
[[Category: Roco]]
 +
[[Category: Serine/threonine-protein kinase]]
 +
[[Category: Transferase]]
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 11 10:51:29 2008''

Revision as of 07:51, 11 June 2008

Image:3d6t.jpg

Template:STRUCTURE 3d6t

Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase


Overview

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of Parkinson's disease (PD). LRRK2 contains a Ras of complex proteins (ROC) domain that may act as a GTPase to regulate its protein kinase activity. The structure of ROC and the mechanism(s) by which it regulates kinase activity are not known. Here, we report the crystal structure of the LRRK2 ROC domain in complex with GDP-Mg(2+) at 2.0-A resolution. The structure displays a dimeric fold generated by extensive domain-swapping, resulting in a pair of active sites constructed with essential functional groups contributed from both monomers. Two PD-associated pathogenic residues, R1441 and I1371, are located at the interface of two monomers and provide exquisite interactions to stabilize the ROC dimer. The structure demonstrates that loss of stabilizing forces in the ROC dimer is likely related to decreased GTPase activity resulting from mutations at these sites. Our data suggest that the ROC domain may regulate LRRK2 kinase activity as a dimer, possibly via the C-terminal of ROC (COR) domain as a molecular hinge. The structure of the LRRK2 ROC domain also represents a signature from a previously undescribed class of GTPases from complex proteins and results may provide a unique molecular target for therapeutics in PD.

About this Structure

3D6T is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase., Deng J, Lewis PA, Greggio E, Sluch E, Beilina A, Cookson MR, Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1499-504. Epub 2008 Jan 29. PMID:18230735 Page seeded by OCA on Wed Jun 11 10:51:29 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3d6t"
Personal tools