The Structure and Dynamics of Tandem WW Domains in a Negative Regulator of Notch Signaling, Suppressor of Deltex
WW domains mediate protein recognition, usually though binding to proline-rich sequences. In many proteins, WW domains occur in tandem arrays. Whether or how individual domains within such arrays cooperate to recognize biological partners is, as yet, poorly characterized. An important question is wh...
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Published in | The Journal of biological chemistry Vol. 279; no. 33; pp. 34991 - 35000 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
13.08.2004
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Subjects | |
Online Access | Get full text |
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Summary: | WW domains mediate protein recognition, usually though binding to proline-rich sequences. In many proteins, WW domains occur
in tandem arrays. Whether or how individual domains within such arrays cooperate to recognize biological partners is, as yet,
poorly characterized. An important question is whether functional diversity of different WW domain proteins is reflected in
the structural organization and ligand interaction mechanisms of their multiple domains. We have determined the solution structure
and dynamics of a pair of WW domains (WW3â4) from a Drosophila Nedd4 family protein called Suppressor of deltex (Su(dx)), a regulator of Notch receptor signaling. We find that the binding
of a type 1 PPPY ligand to WW3 stabilizes the structure with effects propagating to the WW4 domain, a domain that is not active
for ligand binding. Both WW domains adopt the characteristic triple-stranded β-sheet structure, and significantly, this is
the first example of a WW domain structure to include a domain (WW4) lacking the second conserved Trp (replaced by Phe). The
domains are connected by a flexible linker, which allows a hinge-like motion of domains that may be important for the recognition
of functionally relevant targets. Our results contrast markedly with those of the only previously determined three-dimensional
structure of tandem WW domains, that of the rigidly oriented WW domain pair from the RNA-splicing factor Prp40. Our data illustrate
that arrays of WW domains can exhibit a variety of higher order structures and ligand interaction mechanisms. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M404987200 |