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PDBsum entry 2rpn
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Structural protein
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PDB id
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2rpn
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References listed in PDB file
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Key reference
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Title
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Structural, Functional, And bioinformatic studies demonstrate the crucial role of an extended peptide binding site for the sh3 domain of yeast abp1p.
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Authors
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E.J.Stollar,
B.Garcia,
P.A.Chong,
A.Rath,
H.Lin,
J.D.Forman-Kay,
A.R.Davidson.
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Ref.
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J Biol Chem, 2009,
284,
26918-26927.
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PubMed id
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Abstract
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SH3 domains, which are among the most frequently occurring protein interaction
modules in nature, bind to peptide targets ranging in length from 7 to more than
25 residues. Although the bulk of studies on the peptide binding properties of
SH3 domains have focused on interactions with relatively short peptides (less
than 10 residues), a number of domains have been recently shown to require much
longer sequences for optimal binding affinity. To gain greater insight into the
binding mechanism and biological importance of interactions between an SH3
domain and extended peptide sequences, we have investigated interactions of the
yeast Abp1p SH3 domain (AbpSH3) with several physiologically relevant 17-residue
target peptide sequences. To obtain a molecular model for AbpSH3 interactions,
we solved the structure of the AbpSH3 bound to a target peptide from the yeast
actin patch kinase, Ark1p. Peptide target complexes from binding partners Scp1p
and Sjl2p were also characterized, revealing that the AbpSH3 uses a common
extended interface for interaction with these peptides, despite K(d) values for
these peptides ranging from 0.3 to 6 mum. Mutagenesis studies demonstrated that
residues across the whole 17-residue binding site are important both for maximal
in vitro binding affinity and for in vivo function. Sequence conservation
analysis revealed that both the AbpSH3 and its extended target sequences are
highly conserved across diverse fungal species as well as higher eukaryotes. Our
data imply that the AbpSH3 must bind extended target sites to function
efficiently inside the cell.
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