PDBsum entry 5e6p

Signaling protein

PDB id: 5e6p

Contents

Protein chains

504 a.a.

75 a.a.

PDB id:

5e6p

Name:

Signaling protein

Title:

Plexinb2 cytoplasmic region/pdz-rhogef pdz domain complex

Structure:

Plexin-b2. Chain: a. Fragment: unp residues 1226-1842. Engineered: yes. Rho guanine nucleotide exchange factor 11. Chain: b. Fragment: pdz domain (unp residues 42-125). Synonym: pdz-rhogef. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: plxnb2. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606.

Resolution:

3.22Å R-factor: 0.256 R-free: 0.297

Authors:

H.G.Pascoe,X.Zhang

Key ref:

H.G.Pascoe et al. (2015). Secondary PDZ domain-binding site on class B plexins enhances the affinity for PDZ-RhoGEF. Proc Natl Acad Sci U S A, 112, 14852-14857. PubMed id: 26627240 DOI: 10.1073/pnas.1508931112

Date:

10-Oct-15 Release date: 18-Nov-15

Protein chain

B2RXS4  (PLXB2_MOUSE) -  Plexin-B2 from Mus musculus

Seq: 1842 a.a.

Struc: 504 a.a.

Protein chain

O15085  (ARHGB_HUMAN) -  Rho guanine nucleotide exchange factor 11 from Homo sapiens

Seq: 1522 a.a.

Struc: 75 a.a.

DOI no: 10.1073/pnas.1508931112

Proc Natl Acad Sci U S A 112:14852-14857 (2015)

PubMed id: 26627240

Secondary PDZ domain-binding site on class B plexins enhances the affinity for PDZ-RhoGEF.

H.G.Pascoe, S.Gutowski, H.Chen, C.A.Brautigam, Z.Chen, P.C.Sternweis, X.Zhang.

ABSTRACT

PDZ domains are abundant protein interaction modules and typically recognize a short motif at the C terminus of their ligands, with a few residues in the motif endowing the binding specificity. The sequence-based rules, however, cannot fully account for the specificity between the vast number of PDZ domains and ligands in the cell. Plexins are transmembrane receptors that regulate processes such as axon guidance and angiogenesis. Two related guanine nucleotide exchange factors (GEFs), PDZ-RhoGEF and leukemia-associated RhoGEF (LARG), use their PDZ domains to bind class B plexins and play critical roles in signaling. Here, we present the crystal structure of the full-length cytoplasmic region of PlexinB2 in complex with the PDZ domain of PDZ-RhoGEF. The structure reveals that, in addition to the canonical C-terminal motif/PDZ interaction, the 3D domain of PlexinB2 forms a secondary interface with the PDZ domain. Our biophysical and cell-based assays show that the secondary interface contributes to the specific interaction between plexin and PDZ-RhoGEF and to signaling by plexin in the cell. Formation of secondary interfaces may be a general mechanism for increasing affinity and specificity of modular domain-mediated interactions.