Reference : Alternative binding modes of proline-rich peptides binding to the GYF domain
Scientific journals : Other
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/3774
Alternative binding modes of proline-rich peptides binding to the GYF domain
English
Gu, Wei mailto []
Kofler, M. [> >]
Antes, I. [> >]
Freund, C. [> >]
Helms, V. [> >]
2005
Biochemistry
American Chemical Society
44
17
6404-6415
Yes (verified by ORBilu)
International
0006-2960
1520-4995
Washington
DC
[en] Recognition of proline-rich sequences plays an important role for the assembly of multiprotein complexes during the course of eukaryotic signal transduction and is mediated by a set of protein folds that share characteristic features. The GYF (glycine-tyrosine-phenylalanine) domain is known as a member of the superfamily of recognition domains for proline-rich sequences. Recent studies on the complexation of the CD2BP2-GYF domain with CD2 peptides showed that the peptide adopts an extended conformation and forms a polyproline type-II helix involving residues Pro4-Pro7 [Freund et al. (2002) EMBO J. 21, 5985-5995]. R/K/GxxPPGxR/K is the key signature for the peptides that bind to the GYF domain [Kofler et at. (2004) J. Biol. Chem. 279, 28292-28297]. In our combined theoretical and experimental study, we show that the peptides adopt a polyproline 11 helical conformation in the unbound form as well as in the complex. From molecular dynamics simulations, we identify a novel binding mode for the G8W mutant and the wild-type peptide (shifted by one proline in register). In contrast, the conformation of the peptide mutant H9M remains close to the experimentally derived wild-type GYF-peptide complex. Possible functional implications of this altered conformation of the bound ligand are discussed in the light of our experimental and theoretical results.
http://hdl.handle.net/10993/3774
10.1021/bi0479914

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