Topography for independent binding of α-helical and PPII-helical ligands to a peroxisomal SH3 domain

被引:67
作者
Douangamath, A
Filipp, FV
Klein, ATJ
Barnett, P
Zou, PJ
Voorn-Brouwer, T
Vega, MC
Mayans, OM
Sattler, M
Distel, B
Wilmanns, M
机构
[1] EMBL Heidelberg, Struct & Computat Biol Programme, D-69117 Heidelberg, Germany
[2] Deutsch Elektronen Synchtrotron, EMBL Hamburg, D-22603 Hamburg, Germany
[3] Univ Amsterdam, Acad Med Ctr, Dept Biochem, NL-1100 DE Amsterdam, Netherlands
关键词
D O I
10.1016/S1097-2765(02)00749-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
While the function of most small signaling domains is confined to binary ligand interactions, the peroxisomal Pex13p SH3 domain has the unique capacity of binding to two different ligands, Pex5p and Pex14p. We have used this domain as a model to decipher its structurally independent ligand binding sites. By the combined use of X-ray crystallography, NMR spectroscopy, and circular dichroism, we show that the two ligands bind in unrelated conformations to patches located at opposite surfaces of this SH3 domain. Mutations in the Pex13p SH3 domain that abolish interactions within the Pex13p-Pex5p interface specifically impair PTS1-dependent protein import into yeast peroxisomes.
引用
收藏
页码:1007 / 1017
页数:11
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