Site-directed mutagenesis and structural modeling of Coq10p indicate the presence of a tunnel for coenzyme Q6 binding

Cleverson Busso; Lucas Bleicher; José Ribamar Ferreira-Júnior; Mario H Barros

doi:10.1016/j.febslet.2010.03.024

Site-directed mutagenesis and structural modeling of Coq10p indicate the presence of a tunnel for coenzyme Q6 binding

FEBS Lett. 2010 Apr 16;584(8):1609-14. doi: 10.1016/j.febslet.2010.03.024. Epub 2010 Mar 18.

Authors

Cleverson Busso¹, Lucas Bleicher, José Ribamar Ferreira-Júnior, Mario H Barros

Affiliation

¹ Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.

PMID: 20303962
DOI: 10.1016/j.febslet.2010.03.024

Abstract

Coq10p is a protein required for coenzyme Q function, but its specific role is still unknown. It is a member of the START domain superfamily that contains a hydrophobic tunnel implicated in the binding of lipophilic molecules. We used site-directed mutagenesis, statistical coupling analysis and molecular modeling to probe structural determinants in the Coq10p putative tunnel. Four point mutations were generated (coq10-K50E, coq10-L96S, coq10-E105K and coq10-K162D) and their biochemical properties analysed, as well as structural consequences. Our results show that all mutations impaired Coq10p function and together with molecular modeling indicate an important role for the Coq10p putative tunnel.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Bacterial Proteins / chemistry*
Bacterial Proteins / genetics
Bacterial Proteins / metabolism*
Cell Respiration
Hydrophobic and Hydrophilic Interactions
Models, Molecular*
Molecular Sequence Data
Mutagenesis, Site-Directed*
Mutation
Protein Conformation
Ubiquinone / metabolism*

Substances

Bacterial Proteins
ubiquinone 6
Ubiquinone