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Published February 2016 | Accepted Version
Journal Article Open

Cytochrome unfolding pathways from computational analysis of crystal structures

Abstract

We have developed a model to study the role of geometrical factors in influencing the early stages of unfolding in three cytochromes: cyt c′, cyt c-b_(562) and cyt c. Each stage in unfolding is quantified by the spatial extension 〈λ_i〉 of n-residue segments, and by their angular extension 〈β_n〉. Similarities and differences between and among the three cytochromes in the unfolding of helical and non-helical regions can be determined by analyzing the data for each signature separately. Definite conclusions can be drawn when spatial and angular changes are considered in tandem. To facilitate comparisons, we present graphical portraits of the three cytochromes at the same stage of unfolding, and in relation to their native state structures. We also display specific segments at different stages of unfolding to illustrate differences in stability of defined domains thereby allowing us to make specific predictions on the unfolding of corresponding internal and terminal helices in cyt c′ and cyt c-b_(562). Our work accords with an earlier experimental report on the presence and persistence of a hydrophobic core in cyt c.

Additional Information

© 2016 Elsevier Inc. Received 1 August 2015; Received in revised form 7 October 2015; Accepted 1 November 2015; Available online 10 November 2015. We wish to acknowledge conversations with a number of colleagues who have provided valuable insights on both the strengths and limitations of the model presented here. Special thanks go to David Eisenberg, who suggested that the development would benefit from a graphical representation of selected results, and to J.R. Winkler. The authors would also like to thank one of the reviewers for drawing attention to one aspect of Ramachandran's (φ, ψ) plots. Financial support for R.A.G.-L. was provided by the Howard Hughes Medical Institute (grant # 52007555) Research Program from Pomona College. The authors would like to thank Pomona College undergraduates Sabari Kumar, Don Chen, Spencer Satz and Neil Chan for their help in developing the images for this paper. The molecular graphics images were produced using the Chimera package from the Computer Graphics Laboratory, University of California, San Francisco (supported by NIH P41 RR-01081). H.B. Gray thanks NIH (DK019038) and the Arnold and Mabel Beckman Foundation (BILRC) for support of the work. Research at the California Institute of Technology was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award R01DK019038 (to H.B.G.).

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August 22, 2023
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