Investigation of the redox-dependent modulation of structure and dynamics in human cytochrome c

Mizue Imai; Tomohide Saio; Hiroyuki Kumeta; Takeshi Uchida; Fuyuhiko Inagaki; Koichiro Ishimori

doi:10.1016/j.bbrc.2015.12.079

Investigation of the redox-dependent modulation of structure and dynamics in human cytochrome c

Biochem Biophys Res Commun. 2016 Jan 22;469(4):978-84. doi: 10.1016/j.bbrc.2015.12.079. Epub 2015 Dec 22.

Authors

Mizue Imai¹, Tomohide Saio², Hiroyuki Kumeta³, Takeshi Uchida², Fuyuhiko Inagaki³, Koichiro Ishimori⁴

Affiliations

¹ Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0810, Japan.
² Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0810, Japan; Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan.
³ Faculty of Advanced Life Science, Hokkaido University, Sapporo 001-0021, Japan.
⁴ Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0810, Japan; Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan. Electronic address: koichiro@sci.hokudai.ac.jp.

PMID: 26718409
DOI: 10.1016/j.bbrc.2015.12.079

Abstract

Redox-dependent changes in the structure and dynamics of human cytochrome c (Cyt c) were investigated by solution NMR. We found significant structural changes in several regions, including residues 23-28 (loop 3), which were further corroborated by chemical shift differences between the reduced and oxidized states of Cyt c. These differences are essential for discriminating redox states in Cyt c by cytochrome c oxidase (CcO) during electron transfer reactions. Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments identified that the region around His33 undergoes conformational exchanges on the μs-ms timescale, indicating significant redox-dependent structural changes. Because His33 is not part of the interaction site for CcO, our data suggest that the dynamic properties of the region, which is far from the interaction site for CcO, contribute to conformational changes during electron transfer to CcO.

Keywords: Cytochrome c; Dynamics; Electron transfer; Solution structure.

Publication types

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

MeSH terms

Binding Sites
Cytochromes c / chemistry*
Cytochromes c / ultrastructure*
Enzyme Activation
Humans
Kinetics
Oxidation-Reduction
Oxygen / chemistry*
Protein Binding
Protein Conformation
Structure-Activity Relationship

Substances

Cytochromes c
Oxygen