4wyu
From Proteopedia
Crystal Structure of Scribble PDZ34 tandem in complex with its target peptide
Structural highlights
Disease[SCRIB_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. Function[SCRIB_HUMAN] Scaffold protein involved in different aspects of polarized cells differentiation regulating epithelial and neuronal morphogenesis. Most probably functions in the establishment of apico-basal cell polarity. May function in cell proliferation regulating progression from G1 to S phase and as a positive regulator of apoptosis for instance during acinar morphogenesis of the mammary epithelium. May also function in cell migration and adhesion and hence regulate cell invasion through MAPK signaling. May play a role in exocytosis and in the targeting synaptic vesicles to synapses. Functions as an activator of Rac GTPase activity.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedTandem-arranged PDZ [PSD-95 (postsynaptic density-95), Dlg (discs large homologue) and ZO-1 (zonula occludens-1)] domains often form structural and functional supramodules with distinct target-binding properties. In the present study, we found that the two PDZ domains within the PDZ34 tandem of Scribble, a cell polarity regulator, tightly pack in a 'front-to-back' mode to form a compact supramodule. Although PDZ4 contains a distorted alphaB/betaB pocket, the attachment of PDZ4 to PDZ3 generates an unexpected interdomain pocket that is adjacent to and integrates with the canonical alphaB/betaB pocket of PDZ3 to form an expanded target-binding groove. The structure of the PDZ34-target peptide complex further demonstrated that the peptide binds to this expanded target-binding groove with its upstream residues anchoring into the interdomain pocket directly. Mutations of the interdomain pocket and disruptions of the PDZ34 supramodule both interfere with its target-binding capacity. Therefore, the interdomain interface between the PDZ34 supramodule is intrinsically required for its target recognition and determines its target-binding specificity. This interdomain interface-mediated specific recognition may represent a novel mode of target recognition and would broaden the target-binding versatility for PDZ supramodules. The supramodular nature and target recognition mode of the PDZ34 tandem found in the present study would also help to identify the new binding partners of Scribble and thus may direct further research on the PDZ domain-mediated assembly of Scribble polarity complexes. Interdomain interface-mediated target recognition by the Scribble PDZ34 supramodule.,Ren J, Feng L, Bai Y, Pei H, Yuan Z, Feng W Biochem J. 2015 May 15;468(1):133-44. doi: 10.1042/BJ20141473. PMID:25734361[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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