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A Dynamic Model of the Proteins that Form the Initial Iron-Sulfur Cluster Biogenesis Machinery in Yeast Mitochondria

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Abstract

The assembly of iron-sulfur clusters (ISCs) in eukaryotes involves the protein Frataxin. Deficits in this protein have been associated with iron inside the mitochondria and impair ISC biogenesis as it is postulated to act as the iron donor for ISCs assembly in this organelle. A pronounced lack of Frataxin causes Friedreich’s Ataxia, which is a human neurodegenerative and hereditary disease mainly affecting the equilibrium, coordination, muscles and heart. Moreover, it is the most common autosomal recessive ataxia. High similarities between the human and yeast molecular mechanisms that involve Frataxin have been suggested making yeast a good model to study that process. In yeast, the protein complex that forms the central assembly platform for the initial step of ISC biogenesis is composed by yeast frataxin homolog, Nfs1–Isd11 and Isu. In general, it is commonly accepted that protein function involves interaction with other protein partners, but in this case not enough is known about the structure of the protein complex and, therefore, how it exactly functions. The objective of this work is to model the protein complex in order to gain insight into structural details that end up with its biological function. To achieve this goal several bioinformatics tools, modeling techniques and protein docking programs have been used. As a result, the structure of the protein complex and the dynamic behavior of its components, along with that of the iron and sulfur atoms required for the ISC assembly, have been modeled. This hypothesis will help to better understand the function and molecular properties of Frataxin as well as those of its ISC assembly protein partners.

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Abbreviations

FRDA:

Friedreich’s Ataxia

ISC:

Iron-sulfur cluster

Yfh1:

Yeast frataxin homolog 1

PDB:

Protein Data Bank

PLP:

Pyridoxal phosphate

VAST:

Vector alignment search tool

TO:

Totally opened

TC:

Totally closed

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Acknowledgments

This research was supported by Grants BIO2007-67904-C02-01, BFU2010-22209-C02-01, MTM2010-14887 from the MCYT (Ministerio de Ciencia y Tecnología, Spain), from the Centre de Referència de R + D de Biotecnologia de la Generalitat de Catalunya, from Fundació La Marató de TV3 101930/31/32/33 and from the Comisión Coordinadora del Interior (Uruguay). The authors thank Mr. Òscar Conchillo for his help with several protein analysis tools and for technical support. This manuscript has been corrected by Mr. Chuck Simmons, a native English-speaking Instructor of English of this University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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  1. A. Gómez

    Present address: Cancer Epigenetics and Biology Program (PEBC), Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), Hospital Duran i Reynals, Av. Gran Via s/n km, 2.7, L’Hospitalet de Llobregat, 08908, Barcelona, Catalonia, Spain

Authors and Affiliations

  1. Departament de Bioquímica i Biologia Molecular, Institut de Biotecnologia i de Biomedicina, Parc de Recerca Universitat Autònoma de Barcelona, 08193, Bellaterra, Barcelona, Catalonia, Spain

    I. Amela, A. Gómez & E. Querol

  2. Departament d’Estadística i Investigació Operativa, Universitat Politècnica de Catalunya, 08034, Barcelona, Catalonia, Spain

    P. Delicado

  3. Laboratorio de Inmunología, Universidad de la República Regional Norte-Salto, Rivera 1350, CP 50000, Salto, Uruguay

    J. Cedano

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Amela, I., Delicado, P., Gómez, A. et al. A Dynamic Model of the Proteins that Form the Initial Iron-Sulfur Cluster Biogenesis Machinery in Yeast Mitochondria. Protein J 32, 183–196 (2013). https://doi.org/10.1007/s10930-013-9475-4

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