Structural variability of peptide deformylase

A. Hrádková1, M. H. Kolář1, J. Kubíček2

1Department of Physical Chemistry, University of Chemistry and Technology, Praha

2Gymnázium, Nad Kavalírkou 1, Praha

hradkova@vscht.cz

The first enzyme that bacterial proteins encounter after their birth is the peptide deformylase (PDF). PDF binds to the ribosome surface and removes the formyl group from the N terminus of the nascent protein, which emerges from the ribosomal exit tunnel. Based upon structure and sequence similarity, PDFs are divided into Type I, II, and III, with Type I being further divided into subgroups IA and IB. Type I PDFs feature a C-terminal α-helix that serves as the connection point between the PDF's catalytic domain and the ribosome's surface. Conversely, Type II PDFs exhibit an intrinsically disordered C-terminal region and the mechanism by which Type II PDFs bind to the ribosome is unknown. Due to sequence divergence of Type III in otherwise conserved motifs in Type I and II, Type III PDFs are suggested to be inactive. In our study, we investigate the folding behaviour of the C-terminal region by conducting all-atom molecular dynamics simulations of PDFs derived from various organisms. Our findings reveal significant differences in the conformational ensembles of the C-termini between Type I and Type II PDFs. We quantified the secondary structure propensities of the simulated systems and found notable differences as well. The catalytic domain of PDF plays a pivotal role in shaping the C-terminal fragments. Our results shed light on the potential binding mode of PDF to the ribosomal surface.

 

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Figure 1. Peptide deformylase 5JEZ

 

This work was supported by the Ministry of Education, Youth and Sports of the Czech Republic through the e-INFRA CZ (ID:90254), and by the Czech Science Foundation (project 23-05764S).