title: Binding mode analysis of a major T3SS translocator protein PopB with its chaperone PcrH from Pseudomonas aeruginosa.
abstract: Pseudomonas aeruginosa, a Gram-negative pathogen uses a specialized set of Type III secretion system (T3SS) translocator proteins to establish virulence in the host cell. An understanding of the factors that govern translocation by the translocator protein-chaperone complex is thus of immense importance. In this work, experimental and computational techniques were used to probe into the structure of the major translocator protein PopB from P. aeruginosa and to identify the important regions involved in functioning of the translocator protein. This study reveals that the binding sites of the common chaperone PcrH, needed for maintenance of the translocator PopB within the bacterial cytoplasm, which are primarily localized within the N-terminal domain. However, disordered and flexible residues located both at the N- and C-terminal domains are also observed to be involved in association with the chaperone. This intrinsic disorderliness of the terminal domains is conserved for all the major T3SS translocator proteins and is functionally important to maintain the intrinsically disordered state of the translocators. Our experimental and computational analyses suggest that a "disorder-to-order" transition of PopB protein might take place upon PcrH binding. The long helical coiled-coil part of PopB protein perhaps helps in pore formation while the flexible apical region is involved in chaperone interaction. Thus, our computational model of translocator protein PopB and its binding analyses provide crucial functional insights into the T3SS translocation mechanism.
authors.affiliation: Division of Structural Biology and Bioinformatics, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, Kolkata, 700 032, West Bengal, India.
authors.forename: Anindyajit
authors.initials: A
authors.lastname: Banerjee
authors.forename: Supratim
authors.initials: S
authors.lastname: Dey
authors.forename: Abhijit
authors.initials: A
authors.lastname: Chakraborty
authors.forename: Aohona
authors.initials: A
authors.lastname: Datta
authors.forename: Abhishek
authors.initials: A
authors.lastname: Basu
authors.forename: Saikat
authors.initials: S
authors.lastname: Chakrabarti
authors.forename: Saumen
authors.initials: S
authors.lastname: Datta
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D001665:Binding Sites; D019295:Computational Biology; D017124:Conserved Sequence; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D058849:Protein Refolding; D011550:Pseudomonas aeruginosa / Q000378:metabolism* / Q000472:pathogenicity; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013499:Surface Properties
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D018832:Molecular Chaperones; D010446:Peptide Fragments; C576076:PopB protein, Pseudomonas aeruginosa; D011994:Recombinant Proteins
keywords: PopB-PcrH; Type III secretion system; chaperone; flexibility; translocator