Monferrer D.,IBMB CSIC |
Tralau T.,University of Manchester |
Kertesz M.A.,University of Manchester |
Kertesz M.A.,University of Sydney |
And 3 more authors.
Molecular Microbiology | Year: 2010
LysR-type transcriptional regulators (LTTRs) constitute the largest family of regulators in prokaryotes. The full-length structures of the LTTR TsaR from Comamonas testosteroni T-2 and its complex with the natural inducer para-toluensulfonate have been characterized by X-ray diffraction. Both ligand-free and complexed forms reveal a dramatically different quaternary structure from that of CbnR from Ralstonia eutropha, or a putative LysR-type regulator from Pseudomonas aeruginosa, the only other determined full-length structures of tetrameric LTTRs. Although all three show a head-to-head tetrameric ring, TsaR displays an open conformation, whereas CbnR and PA01-PR present additional contacts in opposing C-terminal domains that close the ring. Such large differences may be due to a broader structural versatility than previously assumed or either, reflect the intrinsic flexibility of tetrameric LTTRs. On the grounds of the sliding dimer hypothesis of LTTR activation, we propose a structural model in which the closed structures could reflect the conformation of a ligand-free LTTR, whereas inducer binding would bring about local changes to disrupt the interface linking the two compact C-terminal domains. This could lead to a TsaR-like, open structure, where the pairs of recognition helices are closer to each other by more than 10. © 2010 Blackwell Publishing Ltd.
Barbany M.,IBMB CSIC |
Morata J.,IBMB CSIC |
Meyer T.,Barcelona Institute for Research in Biomedicine |
Meyer T.,Max Planck Institute for Chemistry |
And 5 more authors.
Proteins: Structure, Function and Bioinformatics | Year: 2012
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. © 2012 Wiley Periodicals, Inc.