This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

2dx1

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 08:23, 11 March 2020

Crystal structure of RhoGEF protein Asef

Structural highlights

2dx1 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT, TOPSAN

Function

[ARHG4_HUMAN] Acts as guanine nucleotide exchange factor (GEF) for RHOA, RAC1 and CDC42 GTPases. Binding of APC may activate RAC1 GEF activity. The APC-ARHGEF4 complex seems to be involved in cell migration as well as in E-cadherin-mediated cell-cell adhesion. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Involved in tumor angiogenesis and may play a role in intestinal adenoma formation and tumor progression.^[1] ^[2] ^[3] ^[4] ^[5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The Rac-specific guanine nucleotide exchange factor (GEF) Asef is activated by binding to the tumor suppressor adenomatous polyposis coli mutant, which is found in sporadic and familial colorectal tumors. This activated Asef is involved in the migration of colorectal tumor cells. The GEFs for Rho family GTPases contain the Dbl homology (DH) domain and the pleckstrin homology (PH) domain. When Asef is in the resting state, the GEF activity of the DH-PH module is intramolecularly inhibited by an unidentified mechanism. Asef has a Src homology 3 (SH3) domain in addition to the DH-PH module. In the present study, the three-dimensional structure of Asef was solved in its autoinhibited state. The crystal structure revealed that the SH3 domain binds intramolecularly to the DH domain, thus blocking the Rac-binding site. Furthermore, the RT-loop and the C-terminal region of the SH3 domain interact with the DH domain in a manner completely different from those for the canonical binding to a polyproline-peptide motif. These results demonstrate that the blocking of the Rac-binding site by the SH3 domain is essential for Asef autoinhibition. This may be a common mechanism in other proteins that possess an SH3 domain adjacent to a DH-PH module.

Crystal structure of the rac activator, Asef, reveals its autoinhibitory mechanism.,Murayama K, Shirouzu M, Kawasaki Y, Kato-Murayama M, Hanawa-Suetsugu K, Sakamoto A, Katsura Y, Suenaga A, Toyama M, Terada T, Taiji M, Akiyama T, Yokoyama S J Biol Chem. 2007 Feb 16;282(7):4238-42. Epub 2006 Dec 26. PMID:17190834^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kawasaki Y, Senda T, Ishidate T, Koyama R, Morishita T, Iwayama Y, Higuchi O, Akiyama T. Asef, a link between the tumor suppressor APC and G-protein signaling. Science. 2000 Aug 18;289(5482):1194-7. PMID:10947987
↑ Kawasaki Y, Sato R, Akiyama T. Mutated APC and Asef are involved in the migration of colorectal tumour cells. Nat Cell Biol. 2003 Mar;5(3):211-5. PMID:12598901 doi:10.1038/ncb937
↑ Hamann MJ, Lubking CM, Luchini DN, Billadeau DD. Asef2 functions as a Cdc42 exchange factor and is stimulated by the release of an autoinhibitory module from a concealed C-terminal activation element. Mol Cell Biol. 2007 Feb;27(4):1380-93. Epub 2006 Dec 4. PMID:17145773 doi:10.1128/MCB.01608-06
↑ Kawasaki Y, Sagara M, Shibata Y, Shirouzu M, Yokoyama S, Akiyama T. Identification and characterization of Asef2, a guanine-nucleotide exchange factor specific for Rac1 and Cdc42. Oncogene. 2007 Dec 6;26(55):7620-267. Epub 2007 Jun 18. PMID:17599059 doi:10.1038/sj.onc.1210574
↑ Kawasaki Y, Tsuji S, Muroya K, Furukawa S, Shibata Y, Okuno M, Ohwada S, Akiyama T. The adenomatous polyposis coli-associated exchange factors Asef and Asef2 are required for adenoma formation in Apc(Min/+)mice. EMBO Rep. 2009 Dec;10(12):1355-62. doi: 10.1038/embor.2009.233. Epub 2009 Nov 6. PMID:19893577 doi:10.1038/embor.2009.233
↑ Murayama K, Shirouzu M, Kawasaki Y, Kato-Murayama M, Hanawa-Suetsugu K, Sakamoto A, Katsura Y, Suenaga A, Toyama M, Terada T, Taiji M, Akiyama T, Yokoyama S. Crystal structure of the rac activator, Asef, reveals its autoinhibitory mechanism. J Biol Chem. 2007 Feb 16;282(7):4238-42. Epub 2006 Dec 26. PMID:17190834 doi:10.1074/jbc.C600234200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2dx1"

@@ Line 1: / Line 1: @@
 ==Crystal structure of RhoGEF protein Asef==
-<StructureSection load='2dx1' size='340' side='right' caption='[[2dx1]], [[Resolution|resolution]] 2.36&Aring;' scene=''>
+<StructureSection load='2dx1' size='340' side='right'caption='[[2dx1]], [[Resolution|resolution]] 2.36&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2dx1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DX1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DX1 FirstGlance]. <br>
@@ Line 30: / Line 30: @@
 ==See Also==
-*[[Rho guanine nucleotide exchange factor|Rho guanine nucleotide exchange factor]]
+*[[Rho guanine nucleotide exchange factor 3D structures|Rho guanine nucleotide exchange factor 3D structures]]
 == References ==
 <references/>
@@ Line 36: / Line 36: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Kato-Murayama, M]]
 [[Category: Murayama, K]]

2dx1

From Proteopedia

Revision as of 08:23, 11 March 2020

Crystal structure of RhoGEF protein Asef

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox