title: Conformational dynamics of Peb4 exhibit "mother's arms" chain model: a molecular dynamics study.
abstract: Peb4 from Campylobacter jejuni is an intertwined dimeric, periplasmic holdase, which also exhibits peptidyl prolyl cis/trans isomerase (PPIase) activity. Peb4 gene deletion alters the outer membrane protein profile and impairs cellular adhesion and biofilm formation for C. jejuni. Earlier crystallographic study has proposed that the PPIase domains are flexible and might form a cradle for holding the substrate and these aspects of Peb4 were explored using sub-microsecond molecular dynamics simulations in solution environment. Our simulations have revealed that PPIase domains are highly flexible and undergo a large structural change where they move apart from each other by 8 nm starting at .5 nm. Further, this large conformational change renders Peb4 as a compact protein with crossed-over conformation, forms a central cavity, which can "cradle" the target substrate. As reported for other chaperone proteins, flexibility of linker region connecting the chaperone and PPIase domains is key to forming the "crossed-over" conformation. The conformational transition of the Peb4 protein from the X-ray structure to the crossed-over conformation follows the "mother's arms" chain model proposed for the FkpA chaperone protein. Our results offer insights into how Peb4 and similar chaperones can use the conformational heterogeneity at their disposal to perform its much-revered biological function.
authors.affiliation: a Department of Biosciences and Bioengineering , Indian Institute of Technology Bombay , Powai, Mumbai 400076 , India.
authors.forename: Sarath Chandra
authors.identifier: http://orcid.org/0000-0003-2019-5311
authors.initials: SC
authors.lastname: Dantu
authors.affiliation: b UM-DAE Centre for Excellence in Basic Science , University of Mumbai , Vidhyanagari Campus, Mumbai 400098 , India.
authors.forename: Sagar
authors.identifier: http://orcid.org/0000-0003-2020-3561
authors.initials: S
authors.lastname: Khavnekar
authors.affiliation: b UM-DAE Centre for Excellence in Basic Science , University of Mumbai , Vidhyanagari Campus, Mumbai 400098 , India.
authors.forename: Avinash
authors.identifier: http://orcid.org/0000-0001-9212-9343
authors.initials: A
authors.lastname: Kale
mesh_terms: D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D016123:Campylobacter jejuni / Q000737:chemistry* / Q000201:enzymology; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D019696:Peptidylprolyl Isomerase / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D040681:Structural Homology, Protein; D013379:Substrate Specificity; D013816:Thermodynamics; D037521:Virulence Factors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C560628:Cj0596 protein, Campylobacter jejuni; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D037521:Virulence Factors; D019696:Peptidylprolyl Isomerase; C068254:FkpA protein, E coli
keywords: chaperone; crossed-over conformation; holdase; molecular dynamics; mother’s arms model