Structural analysis of WW domains and design of a WW prototype.
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 beta-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 beta-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.
Macias
M J
MJ
Forschungsinstitut für Molekulare Pharmakologie, Alfred-Kowalke-Str. 4, 10315 Berlin, Germany. macias@EMBL-Heidelberg.de
Gervais
V
V
Civera
C
C
Oschkinat
H
H
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics; D002942:Circular Dichroism; D017124:Conserved Sequence / Q000235:genetics; D050556:Fatty Acid-Binding Proteins; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment; D013816:Thermodynamics; D014461:Ultracentrifugation
D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; C106410:Fnbp1 protein, mouse; D005656:Fungal Proteins; D010446:Peptide Fragments