Protein species and moonlighting proteins: Very small changes in a protein's covalent structure can change its biochemical function
journal contributionposted on 2018-02-11, 00:00 authored by C.J. Jeffery
In the past few decades, hundreds of moonlighting proteins have been identified that perform two or more distinct and physiologically relevant biochemical or biophysical functions that are not due to gene fusions, multiple RNA splice variants, or pleiotropic effects. For this special issue on protein species, this article discusses three topics related to moonlighting proteins that illustrate how small changes or differences in protein covalent structures can result in different functions. Examples are given of moonlighting proteins that switch between functions after undergoing post-translational modifications (PTMs), proteins that share high levels of amino acid sequence identity to a moonlighting protein but share only one of its functions, and several "neomorphic moonlighting proteins" in which a single amino acid mutation results in the addition of a new function. Biological significance: For this special issue on protein species, this article discusses three topics related to moonlighting proteins: Post-translational modifications (PTMs) that can cause a switch between functions, homologs that share only one of multiple functions, and proteins in which a single amino acid mutation results in the creation of a new function. The examples included illustrate that even in an average protein of hundreds of amino acids, a relatively small difference in sequence or PTMs can result in a large difference in function, which can be important in predicting protein functions, regulation of protein functions, and in the evolution of new functions.
Publisher StatementNOTICE: This is the author’s version of a work that was accepted for publication in Journal of Proteomics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Proteomics, Volume 134, February 16, 2016, Pages 19-24 DOI: 10.1016/j.jprot.2015.10.003