WW Domain

This is a very simple domain that can bind peptides containing several Proline residues. It often works in tandem with other modules.

The 4 consecutive proline residues are colored violet. The WW domain is colored yellow, and consists primarily of 3 antiparallel beta strands.

Solution structures of the YAP65 WW domain and the variant L30 K in complex with the peptides GTPPPPYTVG, N-(n-octyl)-GPPPY and PLPPY and the application of peptide libraries reveal a minimal binding epitope.

Pires JR, Taha-Nejad F, Toepert F, Ast T, Hoffmüller U, Schneider-Mergener J, Kühne R, Macias MJ, Oschkinat H.
J Mol Biol. 2001 Dec 14;314(5):1147-56.

(PubMed)

1jmq (PDB)

Versatile communication strategies among tandem WW domain repeats.
Dodson EJ, Fishbain-Yoskovitz V, Rotem-Bamberger S, Schueler-Furman O.
Exp Biol Med (Maywood). 2015 Mar;240(3):351-60. doi: 10.1177/1535370214566558. Epub 2015 Feb 20. Review.
PMID: 25710931 Free PMC Article

Abstract
Interactions mediated by short linear motifs in proteins play major roles in regulation of cellular homeostasis since their transient nature allows for easy modulation. We are still far from a full understanding and appreciation of the complex regulation patterns that can be, and are, achieved by this type of interaction. The fact that many linear-motif-binding domains occur in tandem repeats in proteins indicates that their mutual communication is used extensively to obtain complex integration of information toward regulatory decisions. This review is an attempt to overview, and classify, different ways by which two and more tandem repeats cooperate in binding to their targets, in the well-characterized family of WW domains and their corresponding polyproline ligands.

WW or WoW: the WW domains in a union of bliss.
Sudol M, Recinos CC, Abraczinskas J, Humbert J, Farooq A.
IUBMB Life. 2005 Dec;57(12):773-8. Review.

Abstract
WW domains are small protein modules that recognize proline-rich peptide motifs or phosphorylated-serine/threonine proline sites in cognate proteins. Within host proteins these modules are joined to other protein domains or to a variety of catalytic domains acting together as adaptors or targeting anchors of enzymes. An important aspect of signaling by WW domains is their ability to recognize their cognate ligands in tandem. Tandem WW domains not only act in a synergistic manner but also appear to chaperone the function of each other. In this review, we focus on structure, function, and mechanism of the tandem WW domains co-operativity as well as independent actions. We emphasize here the implications of tandem arrangement and cooperative function of the domains for signaling pathways.