4WYT

Crystal Structure of Scribble PDZ34 tandem at 2.6 Angstroms

Summary for 4WYT

• Entry DOI: 10.2210/pdb4wyt/pdb
• Descriptor: Protein scribble homolog, CHLORIDE ION (3 entities in total)
• Functional Keywords: pdz tandem, structural protein
• Biological source: Homo sapiens (Human)
• Cellular location: Cell membrane; Peripheral membrane protein: Q14160
• Total number of polymer chains: 1
• Total formula weight: 22278.63

Authors

Ren, J.Q.,Feng, W. (deposition date: 2014-11-18, release date: 2015-10-21, Last modification date: 2023-11-08)

Primary citation

Ren, J.,Feng, L.,Bai, Y.,Pei, H.,Yuan, Z.,Feng, W.
Interdomain interface-mediated target recognition by the Scribble PDZ34 supramodule.
Biochem.J., 468:133-144, 2015

PubMed Abstract: Tandem-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 αB/βB pocket, the attachment of PDZ4 to PDZ3 generates an unexpected interdomain pocket that is adjacent to and integrates with the canonical αB/βB 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.

PubMed: 25734361
DOI: 10.1042/BJ20141473

Experimental method

X-RAY DIFFRACTION (2.6 Å)