From Proteopedia

Jump to: navigation, search
3nmw, resolution 1.60Å ()
Non-Standard Residues:
Gene: APC variant protein (Homo sapiens)
Related: 3nmx, 3nmz

Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml

Crytal structure of armadillo repeats domain of APC

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.

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:021788986

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

About this Structure

3nmw is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Proteopedia Page Contributors and Editors (what is this?)


Personal tools