title: Conservation and specialization in PAS domain dynamics.
abstract: The PAS (Per-ARNT-Sim) superfamily is presented as a well-suited study case to demonstrate how comparison of functional motions among distant homologous proteins with conserved fold characteristics may give insight into their functional specialization. Based on the importance of structural flexibility of the receptive structures in anticipating the signal-induced conformational changes of these sensory systems, the dynamics of these structures were analysed. Molecular dynamics was proved to be an effective method to obtain a reliable picture of the dynamics of the crystal structures of HERG, phy3, PYP and FixL, provided that an extensive conformational space sampling is performed. Other reliable sources of dynamic information were the ensembles of NMR structures of hPASK, HIF-2alpha and PYP. Essential dynamics analysis was successfully employed to extract the relevant information from the sampled conformational spaces. Comparison of motion patterns in the essential subspaces, based on the structural alignment, allowed identification of the specialized region in each domain. This appears to be evolved in the superfamily by following a specific trend, that also suggests the presence of a limited number of general solutions adopted by the PAS domains to sense external signals. These findings may give insight into unknown mechanisms of PAS domains and guide further experimental studies.
authors.affiliation: Dipartimento di Scienze dell'Ambiente e del Territorio, Università degli Studi di Milano-Bicocca, Piazza della Scienza 1, 20126 Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pandini
authors.forename: L
authors.initials: L
authors.lastname: Bonati
mesh_terms: D035681:Adiantum; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D051792:Basic Helix-Loop-Helix Proteins; D027682:Cation Transport Proteins / Q000737:chemistry; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D020587:Ectothiorhodospira / Q000378:metabolism; D051638:Ether-A-Go-Go Potassium Channels; D006420:Hemeproteins / Q000737:chemistry; D000071677:Histidine Kinase; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015233:Models, Statistical; D008969:Molecular Sequence Data; D009068:Movement; D010786:Photoreceptor Cells / Q000737:chemistry; D020283:Photoreceptors, Microbial / Q000737:chemistry; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D015534:Trans-Activators / Q000737:chemistry; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D001426:Bacterial Proteins; D051792:Basic Helix-Loop-Helix Proteins; D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; D006420:Hemeproteins; D000071677:Histidine Kinase; D008024:Ligands; D020283:Photoreceptors, Microbial; D024642:Potassium Channels, Voltage-Gated; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D015534:Trans-Activators; D000099162:Endothelial PAS Domain-Containing Protein 1; C092509:KCNH6 protein, human; C050162:photoactive yellow protein, Bacteria; C116037:PAS domain kinases; C067929:FixL protein, Bacteria