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Structural analysis of WW domains and design of a WW prototype

Nature Structural Biology volume 7, pages 375–379 (2000)Cite this article

Abstract

Two new NMR structures of WW domains, the mouse formin binding protein and a putative 84.5 kDa protein from Saccharomyces cerevisiae, show that this domain, only 35 amino acids in length, defines the smallest monomeric triple-stranded antiparallel β-sheet protein domain that is stable in the absence of disulfide bonds, tightly bound ions or ligands. The structural roles of conserved residues have been studied using site-directed mutagenesis of both wild type domains. Crucial interactions responsible for the stability of the WW structure have been identified. Based on a network of highly conserved long range interactions across the β-sheet structure that supports the WW fold and on a systematic analysis of conserved residues in the WW family, we have designed a folded prototype WW sequence.

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Figure 1: Analysis of WW sequences.
Figure 2: Pattern of secondary structure NOEs observed for Yap65WW (black), FBP28WW (green), YJQ8WW (red) and the WW prototype (blue).
Figure 3: Structures of the a, FBP28WW, b, YJQ8WW, and c, WW prototype domains.
Figure 4: Spectroscopic properties of the WW prototype.

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Acknowledgements

We thank P. Chambon and the IGBMC-LGME-U.184-ULP for the mouse embryonic day 10 cDNA library, J. Ashurst and S. Moulton for sample preparation, M. Hyvönen for the pGAT2 expression vector and Bruker Analytik GMBH Karlsruhe for measurement time on the DRX-800 MHz spectrometer. The authors are very grateful to J. Castresana, H. Domingues, J. Dixon and R. Wade for useful comments. C.C. was supported by a grant from the Spanish Ministerio de Educacion y Cultura.

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  1. Virginie Gervais

    Present address: École supérieure de Biotechnologie-CNRS-UPR 9003, Boulevard Sébastien Brant, Pole API, 67400, Strasbourg-Illkirch, France

Authors and Affiliations

  1. Forschungsinstitut für Molekulare Pharmakologie, Alfred-Kowalke-Str. 4, Berlin, 10315, Germany

    Maria J. Macias, Virginie Gervais & Hartmut Oschkinat

  2. European Molecular Biology Laboratory, Meyerhofstr. 1, Heidelberg, 69117, Germany

    Maria J. Macias, Virginie Gervais & Concepcion Civera

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  1. Maria J. Macias
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  4. Hartmut Oschkinat
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Correspondence to Maria J. Macias or Hartmut Oschkinat.

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Macias, M., Gervais, V., Civera, C. et al. Structural analysis of WW domains and design of a WW prototype. Nat Struct Mol Biol 7, 375–379 (2000). https://doi.org/10.1038/75144

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