PDBsum entry 4yjl

Cell adhesion/protein binding

PDB id: 4yjl

Contents

Protein chains

(+ 0 more) 337 a.a.

(+ 0 more) 13 a.a.

Ligands

EDO ×37

Waters ×2397

PDB id:

4yjl

Name:

Cell adhesion/protein binding

Title:

Crystal structure of apc-arm in complexed with amer1-a2

Structure:

Adenomatous polyposis coli protein. Chain: a, b, c, d, e, f. Fragment: arm domain, unp residues 407-751. Synonym: protein apc,deleted in polyposis 2.5. Engineered: yes. Apc membrane recruitment protein 1. Chain: g, h, i, j, k, l. Fragment: unp residues 496-508. Synonym: amer1,protein fam123b,wilms tumor gene on the x chromosome

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: apc. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: this sequence occurs naturally in humans.

Resolution:

2.10Å R-factor: 0.208 R-free: 0.225

Authors:

Z.Zhang,Y.Xiao,G.Wu

Key ref:

Z.Zhang et al. (2015). Structures of the APC-ARM domain in complexes with discrete Amer1/WTX fragments reveal that it uses a consensus mode to recognize its binding partners. Cell Discov, 1, 15016. PubMed id: 27462415 DOI: 10.1038/celldisc.2015.16

Date:

03-Mar-15 Release date: 09-Mar-16

Protein chains

P25054  (APC_HUMAN) -  Adenomatous polyposis coli protein from Homo sapiens

Seq: 2843 a.a.

Struc: 337 a.a.*

Protein chains

Q5JTC6  (AMER1_HUMAN) -  APC membrane recruitment protein 1 from Homo sapiens

Seq: 1135 a.a.

Struc: 13 a.a.

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

DOI no: 10.1038/celldisc.2015.16

Cell Discov 1:15016 (2015)

PubMed id: 27462415

Structures of the APC-ARM domain in complexes with discrete Amer1/WTX fragments reveal that it uses a consensus mode to recognize its binding partners.

Z.Zhang, S.Akyildiz, Y.Xiao, Z.Gai, Y.An, J.Behrens, G.Wu.

ABSTRACT

The tumor suppressor APC employs its conserved armadillo repeat (ARM) domain to recognize many of its binding partners, including Amer1/WTX, which is mutated in Wilms' tumor and bone overgrowth syndrome. The APC-Amer1 complex has important roles in regulating Wnt signaling and cell adhesion. Three sites A1, A2, and A3 of Amer1 have been reported to mediate its interaction with APC-ARM. In this study, crystal structures of APC-ARM in complexes with Amer1-A1, -A2, and -A4, which is newly identified in this work, were determined. Combined with our GST pull-down, yeast two-hybrid, and isothermal titration calorimetry (ITC) assay results using mutants of APC and Amer1 interface residues, our structures demonstrate that Amer1-A1, -A2, and -A4, as well as other APC-binding proteins such as Asef and Sam68, all employ a common recognition pattern to associate with APC-ARM. In contrast, Amer1-A3 binds to the C-terminal side of APC-ARM through a bipartite interaction mode. Composite mutations on either APC or Amer1 disrupting all four interfaces abrogated their association in cultured cells and impaired the membrane recruitment of APC by Amer1. Our study thus comprehensively elucidated the recognition mechanism between APC and Amer1, and revealed a consensus recognition sequence employed by various APC-ARM binding partners.