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

Alice Douangamath; Fabian V. Filipp; André T.J. Klein; Phil Barnett; Peijian Zou; Tineke Voorn-Brouwer; M. Cristina Vega; Olga M. Mayans; Michael Sattler; Ben Distel; Matthias Wilmanns

doi:10.1016/S1097-2765(02)00749-9

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

Alice Douangamath, Fabian V. Filipp, André T.J. Klein, Phil Barnett, Peijian Zou, Tineke Voorn-Brouwer, M. Cristina Vega, Olga M. Mayans, Michael Sattler, Ben Distel, Matthias Wilmanns

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73 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	1007-1017
Number of pages	11
Journal	Molecular Cell
Volume	10
Issue number	5
DOIs	https://doi.org/10.1016/S1097-2765(02)00749-9
State	Published - 1 Nov 2002
Externally published	Yes

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@article{5ccff2a6df544dd6a102c377154f868e,

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

abstract = "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.",

author = "Alice Douangamath and Filipp, {Fabian V.} and Klein, {Andr{\'e} T.J.} and Phil Barnett and Peijian Zou and Tineke Voorn-Brouwer and Vega, {M. Cristina} and Mayans, {Olga M.} and Michael Sattler and Ben Distel and Matthias Wilmanns",

note = "Funding Information: We would like to thank Katja Schirwitz and Gunter Stier for advice with protein expression and purification. This work was supported by a grant of the Deutsche Forschungsgemeinschaft to M.W. (WI 1058/4-1) and by the EU Biotechnology Programme to B.D. and M.W. (BIO-CT97-2180). This contribution is dedicated to the memory of Matti Saraste. ",

year = "2002",

month = nov,

day = "1",

doi = "10.1016/S1097-2765(02)00749-9",

language = "English",

volume = "10",

pages = "1007--1017",

journal = "Molecular Cell",

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publisher = "Cell Press",

number = "5",

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TY - JOUR

T1 - Topography for independent binding of α-helical and PPII-helical ligands to a peroxisomal SH3 domain

AU - Douangamath, Alice

AU - Filipp, Fabian V.

AU - Klein, André T.J.

AU - Barnett, Phil

AU - Zou, Peijian

AU - Voorn-Brouwer, Tineke

AU - Vega, M. Cristina

AU - Mayans, Olga M.

AU - Sattler, Michael

AU - Distel, Ben

AU - Wilmanns, Matthias

N1 - Funding Information: We would like to thank Katja Schirwitz and Gunter Stier for advice with protein expression and purification. This work was supported by a grant of the Deutsche Forschungsgemeinschaft to M.W. (WI 1058/4-1) and by the EU Biotechnology Programme to B.D. and M.W. (BIO-CT97-2180). This contribution is dedicated to the memory of Matti Saraste.

PY - 2002/11/1

Y1 - 2002/11/1

N2 - 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.

AB - 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.

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U2 - 10.1016/S1097-2765(02)00749-9

DO - 10.1016/S1097-2765(02)00749-9

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C2 - 12453410

AN - SCOPUS:18744383603

SN - 1097-2765

VL - 10

SP - 1007

EP - 1017

JO - Molecular Cell

JF - Molecular Cell

IS - 5

ER -

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

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