title: Molecular dynamics simulation of SRP GTPases: towards an understanding of the complex formation from equilibrium fluctuations.
abstract: Signal recognition particle (SRP) and its receptor (SR) play essential role in the SRP-dependent protein targeting pathway. They interact with one another to precisely regulate the targeting reaction. The mechanism of this interaction consists of at least two discrete conformational states: complex formation and GTPase activation. Although structural studies have provided valuable insights into the understanding of the SRP-SR interaction, it still remains unclear that how SRP and SR GTPases use their intrinsic conformational flexibilities to exert multiple allosteric regulations on this interaction process. Here, we use computational simulations to present the dynamic behavior of the SRP GTPases at an atomic level to gain further understanding of SRP-SR interaction. We show that: (i) equilibrium conformational fluctuations contain a cooperative inter- and intradomain structural rearrangements that are functionally relevant to complex formation, (ii) a series of residues in different domains are identified to correlate with each other during conformational rearrangements, and (iii) alpha 3 and alpha 4 helices at domain interface actively rearrange their relative conformation to function as a bridge between the N domain and the core region of the G domain. These results, in addition to structural studies, would harness our understanding of the molecular mechanism for SRP and SR interaction.
authors.affiliation: State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning, 116023, China.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Yang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Keli
authors.initials: K
authors.lastname: Han
mesh_terms: D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D019295:Computational Biology; D030562:Databases, Protein; D020558:GTP Phosphohydrolases / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D025341:Principal Component Analysis; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D012329:RNA, Bacterial / Q000737:chemistry; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry*; D018000:Receptors, Peptide / Q000737:chemistry*; D016415:Sequence Alignment; D018271:Signal Recognition Particle; D040681:Structural Homology, Protein; D013824:Thermus / Q000201:enzymology
chemical_list: C409968:4.5S RNA; D001426:Bacterial Proteins; C087406:FtsY protein, Bacteria; D012329:RNA, Bacterial; D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide; D018271:Signal Recognition Particle; C036318:signal peptide receptor; D020558:GTP Phosphohydrolases