Structural bases for the interaction of frataxin with the central components of iron-sulphur cluster assembly

被引：152

作者：

Prischi, Filippo ^{[1
]}

Konarev, Petr V. ^{[2
]}

Iannuzzi, Clara ^{[1
]}

Pastore, Chiara ^{[1
]}

Adinolfi, Salvatore ^{[1
]}

Martin, Stephen R. ^{[1
]}

Svergun, Dmitri I. ^{[2
]}

Pastore, Annalisa ^{[1
]}

机构：

[1] Natl Inst Med Res, London NW7 1AA, England

[2] DESY, EMBL, D-22603 Hamburg, Germany

来源：

NATURE COMMUNICATIONS | 2010年 / 1卷

基金：

英国医学研究理事会;

关键词：

ESCHERICHIA-COLI CYAY; CRYSTAL-STRUCTURE; BIOLOGICAL MACROMOLECULES; CYSTEINE DESULFURASE; SOLUTION SCATTERING; BINDING PROPERTIES; SCAFFOLD PROTEIN; 4FE-4S CLUSTERS; 2FE-2S CLUSTERS; YEAST FRATAXIN;

D O I：

10.1038/ncomms1097

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Reduced levels of frataxin, an essential protein of as yet unknown function, are responsible for causing the neurodegenerative pathology Friedreich's ataxia. Independent reports have linked frataxin to iron-sulphur cluster assembly through interactions with the two central components of this machinery: desulphurase Nfs1/IscS and the scaffold protein Isu/IscU. In this study, we use a combination of biophysical methods to define the structural bases of the interaction of CyaY (the bacterial orthologue of frataxin) with the IscS/IscU complex. We show that CyaY binds IscS as a monomer in a pocket between the active site and the IscS dimer interface. Recognition does not require iron and occurs through electrostatic interactions of complementary charged residues. Mutations at the complex interface affect the rates of enzymatic cluster formation. CyaY binding strengthens the affinity of the IscS/IscU complex. Our data suggest a new paradigm for understanding the role of frataxin as a regulator of IscS functions.

引用

页数：10

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