3nmx
From Proteopedia
(Difference between revisions)
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==Crystal structure of APC complexed with Asef== | ==Crystal structure of APC complexed with Asef== | ||
| - | <StructureSection load='3nmx' size='340' side='right' caption='[[3nmx]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='3nmx' size='340' side='right'caption='[[3nmx]], [[Resolution|resolution]] 2.30Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3nmx]] is a 6 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=3NMX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NMX FirstGlance]. <br> | <table><tr><td colspan='2'>[[3nmx]] is a 6 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=3NMX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NMX FirstGlance]. <br> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/ARHG4_HUMAN 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.<ref>PMID:10947987</ref> <ref>PMID:12598901</ref> <ref>PMID:17145773</ref> <ref>PMID:17599059</ref> <ref>PMID:19893577</ref> | [[http://www.uniprot.org/uniprot/ARHG4_HUMAN 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.<ref>PMID:10947987</ref> <ref>PMID:12598901</ref> <ref>PMID:17145773</ref> <ref>PMID:17599059</ref> <ref>PMID:19893577</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Adenomatous polyposis coli (APC) regulates cell-cell adhesion and cell migration through activating the APC-stimulated guanine nucleotide-exchange factor (GEF; Asef), which is usually autoinhibited through the binding between its Src homology 3 (SH3) and Dbl homology (DH) domains. The APC-activated Asef stimulates the small GTPase Cdc42, which leads to decreased cell-cell adherence and enhanced cell migration. In colorectal cancers, truncated APC constitutively activates Asef and promotes cancer cell migration and angiogenesis. Here, we report crystal structures of the human APC/Asef complex. We find that the armadillo repeat domain of APC uses a highly conserved surface groove to recognize the APC-binding region (ABR) of Asef, conformation of which changes dramatically upon binding to APC. Key residues on APC and Asef for the complex formation were mutated and their importance was demonstrated by binding and activity assays. Structural superimposition of the APC/Asef complex with autoinhibited Asef suggests that the binding between APC and Asef might create a steric clash between Asef-DH domain and APC, which possibly leads to a conformational change in Asef that stimulates its GEF activity. Our structures thus elucidate the molecular mechanism of Asef recognition by APC, as well as provide a potential target for pharmaceutical intervention against cancers. | ||
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| + | Structural basis for the recognition of Asef by adenomatous polyposis coli.,Zhang Z, Chen L, Gao L, Lin K, Zhu L, Lu Y, Shi X, Gao Y, Zhou J, Xu P, Zhang J, Wu G Cell Res. 2012 Feb;22(2):372-86. doi: 10.1038/cr.2011.119. Epub 2011 Jul 26. PMID:21788986<ref>PMID:21788986</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 3nmx" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==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 == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Chen, L]] | [[Category: Chen, L]] | ||
[[Category: Gao, L]] | [[Category: Gao, L]] | ||
Revision as of 09:51, 25 December 2019
Crystal structure of APC complexed with Asef
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