title: Allosteric communication in cysteinyl tRNA synthetase: a network of direct and indirect readout.
abstract: Protein structure networks are constructed for the identification of long-range signaling pathways in cysteinyl tRNA synthetase (CysRS). Molecular dynamics simulation trajectory of CysRS-ligand complexes were used to determine conformational ensembles in order to gain insight into the allosteric signaling paths. Communication paths between the anticodon binding region and the aminoacylation region have been identified. Extensive interaction between the helix bundle domain and the anticodon binding domain, resulting in structural rigidity in the presence of tRNA, has been detected. Based on the predicted model, six residues along the communication paths have been examined by mutations (single and double) and shown to mediate a coordinated coupling between anticodon recognition and activation of amino acid at the active site. This study on CysRS clearly shows that specific key residues, which are involved in communication between distal sites in allosteric proteins but may be elusive in direct structure analysis, can be identified from dynamics of protein structure networks.
authors: Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
authors: Amit
authors: A
authors: Ghosh
authors: Reiko
authors: R
authors: Sakaguchi
authors: Cuiping
authors: C
authors: Liu
authors: Saraswathi
authors: S
authors: Vishveshwara
authors: Ya-Ming
authors: YM
authors: Hou
mesh_terms: D000494:Allosteric Regulation / Q000502:physiology; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000926:Anticodon / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011487:Protein Conformation; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012350:RNA, Transfer, Cys / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000926:Anticodon; D029968:Escherichia coli Proteins; D012329:RNA, Bacterial; D012350:RNA, Transfer, Cys; D000604:Amino Acyl-tRNA Synthetases; C019975:cysteinyl-tRNA synthetase