Characterization of the impact of alternative splicing on protein dynamics: the cases of glutathione S-transferase and ectodysplasin-A isoforms.

TitleCharacterization of the impact of alternative splicing on protein dynamics: the cases of glutathione S-transferase and ectodysplasin-A isoforms.
Publication TypeJournal Article
Year of Publication2012
AuthorsBarbany, Montserrat, Morata Jordi, Meyer Tim, Lois Sergi, Orozco Modesto, and de la Cruz Xavier
JournalProteins
Volume80
Pagination2235-49
Date Published2012 Aug
ISSN1097-0134
KeywordsAlternative Splicing, Amino Acid Sequence, Animals, Anopheles, Binding Sites, Ectodysplasins, Glutathione Transferase, Humans, Molecular Dynamics Simulation, Molecular Sequence Data, Protein Conformation, Protein Isoforms, Sequence Alignment, Thermodynamics
Abstract

Recent studies have shown how alternative splicing (AS), the process by which eukaryotic genes express more than one product, affects protein sequence and structure. However, little information is available on the impact of AS on protein dynamics, a property fundamental for protein function. In this work, we have addressed this issue using molecular dynamics simulations of the isoforms of two model proteins: glutathione S-transferase and ectodysplasin-A. We have found that AS does not have a noticeable impact on global or local structure fluctuations. We have also found that, quite interestingly, AS has a significant effect on the coupling between key structural elements such as surface cavities. Our results provide the first atom-level view of the impact of AS on protein dynamics, as far as we know. They can contribute to refine our present view of the relationship between AS and protein disorder and, more importantly, they reveal how AS may modify structural dynamic couplings in proteins.

DOI10.1002/prot.24112