title: Hydrophobic collapse of trigger factor monomer in solution.
abstract: Trigger factor (TF) is a chaperone, found in bacterial cells and chloroplasts, that interacts with nascent polypeptide chains to suppress aggregation. While its crystal structure has been resolved, the solution structure and dynamics are largely unknown. We performed multiple molecular dynamics simulations on Trigger factor in solution, and show that its tertiary domains display collective motions hinged about inter-domain linkers with minimal or no loss in secondary structure. Moreover, we find that isolated TF typically adopts a collapsed state, with the formation of domain pairs. This collapse of TF in solution is induced by hydrophobic interactions and stabilised by hydrophilic contacts. To determine the nature of the domain interactions, we analysed the hydrophobicity of the domain surfaces by using the hydrophobic probe method of Acharya et al., as the standard hydrophobicity scales predictions are limited due to the complex environment. We find that the formation of domain pairs changes the hydrophobic map of TF, making the N-terminal and arm2 domain pair more hydrophilic and the head and arm1 domain pair more hydrophobic. These insights into the dynamics and interactions of the TF domains are important to eventually understand chaperone-substrate interactions and chaperone function.
authors.affiliation: van 't Hoff Institute of Molecular Sciences, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Kushagra
authors.initials: K
authors.lastname: Singhal
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Vreede
authors.forename: Alireza
authors.initials: A
authors.lastname: Mashaghi
authors.forename: Sander J
authors.initials: SJ
authors.lastname: Tans
authors.forename: Peter G
authors.initials: PG
authors.lastname: Bolhuis
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry*; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D012996:Solutions
chemical_list: D001426:Bacterial Proteins; D018832:Molecular Chaperones; D012996:Solutions
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