5e6p
PlexinB2 cytoplasmic region/PDZ-RhoGEF PDZ domain complexPlexinB2 cytoplasmic region/PDZ-RhoGEF PDZ domain complex
Structural highlights
FunctionPLXB2_MOUSE Cell surface receptor for SEMA4C, SEMA4D and SEMA4G that plays an important role in cell-cell signaling. Binding to class 4 semaphorins promotes downstream activation of RHOA and phosphorylation of ERBB2 at 'Tyr-1248'. Required for normal differentiation and migration of neuronal cells during brain corticogenesis and for normal embryonic brain development. Regulates the migration of cerebellar granule cells in the developing brain. Plays a role in RHOA activation and subsequent changes of the actin cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. May modulate the activity of RAC1 and CDC42. Down-regulates macrophage migration in wound-healing assays (in vitro).[1] [2] [3] [4] Publication Abstract from PubMedPDZ 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. Secondary PDZ domain-binding site on class B plexins enhances the affinity for PDZ-RhoGEF.,Pascoe HG, Gutowski S, Chen H, Brautigam CA, Chen Z, Sternweis PC, Zhang X Proc Natl Acad Sci U S A. 2015 Dec 1;112(48):14852-7. doi:, 10.1073/pnas.1508931112. Epub 2015 Nov 16. PMID:26627240[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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