The binding of the PDZ tandem of syntenin to target proteins.

Abstract:

:PDZ domains are among the most abundant protein modules in the known genomes. Their main function is to provide scaffolds for membrane-associated protein complexes by binding to the cytosolic, C-terminal fragments of receptors, channels, and other integral membrane proteins. Here, using both heteronuclear NMR and single crystal X-ray diffraction, we show how peptides with different sequences, including those corresponding to the C-termini of syndecan, neurexin, and ephrin B, can simultaneously bind to both PDZ domains of the scaffolding protein syntenin. The PDZ2 domain binds these peptides in the canonical fashion, and an induced fit mechanism allows for the accommodation of a range of side chains in the P(0) and P(-)(2) positions. However, binding to the PDZ1 domain requires that the target peptide assume a noncanonical conformation. These data help explain how syntenin, and perhaps other PDZ-containing proteins, may preferentially bind to dimeric and clustered targets, and provide a mechanistic explanation for the previously reported cooperative ligand binding by syntenin's two PDZ domains.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Grembecka J,Cierpicki T,Devedjiev Y,Derewenda U,Kang BS,Bushweller JH,Derewenda ZS

doi

10.1021/bi052225y

subject

Has Abstract

pub_date

2006-03-21 00:00:00

pages

3674-83

issue

11

eissn

0006-2960

issn

1520-4995

journal_volume

45

pub_type

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