142
Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session II
89-POS
Board 42
Discovering Allosteric Communication Pathways on the Bacterial Ribosome: from
Decoding Center to Peptidyl Transferase Center
Pelin Uzun
, Ozge Kurkcuoglu-Levitas.
Istanbul Technical University, Istanbul, Turkey.
Ribosome, a molecular machine synthesizing proteins in the cell, is mainly composed of small
and large subunits (called 30S and 50S in bacteria) connected by multiple intersubunit bridges.
Elucidating the communication pathways responsible for information transport among distant
functional sites on the subunits is critical both to understand the functional mechanisms of the
complex and to develop new antibacterial therapeutics targeting the ribosome. Various studies
indicate sophisticated allosteric communication mechanisms between numerous functional sites
of the complex carefully employed during the translation process, such as between the decoding
center (DC), which is responsible for decoding genetic code on 30S, and the peptidyl transferase
center (PTC), which mediates the peptide bond synthesis on 50S
1
. In this study, three different
crystal ribosome structures of Thermus Thermophilus are investigated to obtain twenty shortest
signaling pathways between DC (residue A1492) and PTC (residues A2451 and G2251). For this
purpose, k-shortest path algorithm
2
is used with the elastic network approach
3
, describing the
ribosome structure as a network of nodes linked by edges. Nodes are placed at alpha-carbon and
phosphor atoms of residues, and length of edges between neighboring node-pairs are calculated
based on atom-atom interactions. Results indicate that major and minor signaling paths exist
between DC and PTC. These paths are composed of highly conserved and/or antibiotic binding
residues, and pass through the B3 intersubunit bridge. Results suggest that B3 bear a critical
position in signal transmission between DC and PTC, and give hints on new druggable sites in
bacterial ribosome.
1) Rakauskaite, R; Dinman, J.D. Nucleic Acids Research, 2008, 36(5), 1497.
2) Yen, J. Y. Management Science, 1971, 17, 712.
3) Kurkcuoglu, O.; Turgut, O. T.; Cansu, S.; Jernigan, R. L.; Doruker, P. Biophysical Journal,
2009, 97, 1178.
