title: Characterization of the impact of alternative splicing on protein dynamics: the cases of glutathione S-transferase and ectodysplasin-A isoforms.
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.
authors.affiliation: Structural Biology Department, IBMB-CSIC, 08028 Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Barbany
authors.forename: Jordi
authors.initials: J
authors.lastname: Morata
authors.forename: Tim
authors.initials: T
authors.lastname: Meyer
authors.forename: Sergi
authors.initials: S
authors.lastname: Lois
authors.forename: Modesto
authors.initials: M
authors.lastname: Orozco
authors.forename: Xavier
authors.initials: X
authors.lastname: de la Cruz
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles; D001665:Binding Sites; D053331:Ectodysplasins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011487:Protein Conformation; D020033:Protein Isoforms; D016415:Sequence Alignment; D013816:Thermodynamics
chemical_list: D053331:Ectodysplasins; D020033:Protein Isoforms; D005982:Glutathione Transferase