TY - JOUR
T1 - Molecular roots of degenerate specificity in syntenin's PDZ2 domain
T2 - Reassessment of the PDZ recognition paradigm
AU - Kang, Beom Sik
AU - Cooper, David R.
AU - Devedjiev, Yancho
AU - Derewenda, Urszula
AU - Derewenda, Zygmunt S.
PY - 2003/7/1
Y1 - 2003/7/1
N2 - Crystal structures of the PDZ2 domain of the scaffolding protein syntenin, both unbound and in complexes with peptides derived from C termini of IL5 receptor (α chain) and syndecan, reveal the molecular roots of syntenin's degenerate specificity. Three distinct binding sites (S0, S-1, and S-2), with affinities for hydrophobic side chains, function in a combinatorial way: S-1 and S-2 act together to bind syndecan, while S0 and S-1 are involved in the binding of IL5Rα. Neither mode of interaction is consistent with the prior classification scheme, which defined the IL5Rα interaction as class I (-S/T-X-φ) and the syndecan interaction as class II (-φ-X-φ). These results, in conjunction with other emerging structural data on PDZ domains, call for a revision of their classification and of the existing model of their mechanism.
AB - Crystal structures of the PDZ2 domain of the scaffolding protein syntenin, both unbound and in complexes with peptides derived from C termini of IL5 receptor (α chain) and syndecan, reveal the molecular roots of syntenin's degenerate specificity. Three distinct binding sites (S0, S-1, and S-2), with affinities for hydrophobic side chains, function in a combinatorial way: S-1 and S-2 act together to bind syndecan, while S0 and S-1 are involved in the binding of IL5Rα. Neither mode of interaction is consistent with the prior classification scheme, which defined the IL5Rα interaction as class I (-S/T-X-φ) and the syndecan interaction as class II (-φ-X-φ). These results, in conjunction with other emerging structural data on PDZ domains, call for a revision of their classification and of the existing model of their mechanism.
UR - http://www.scopus.com/inward/record.url?scp=0037816293&partnerID=8YFLogxK
U2 - 10.1016/S0969-2126(03)00125-4
DO - 10.1016/S0969-2126(03)00125-4
M3 - Article
C2 - 12842047
AN - SCOPUS:0037816293
SN - 0969-2126
VL - 11
SP - 845
EP - 853
JO - Structure
JF - Structure
IS - 7
ER -