dependency map of proteins in the small ribosomal subunit依赖地图小核糖体蛋白质的亚基.pdfVIP

Dependency Map of Proteins in the Small Ribosomal Subunit Kay Hamacher1,2*, Joanna Trylska1,2,3, J. Andrew McCammon1,2,4 1 Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, United States of America, 2 Center for Theoretical Biological Physics, University of California San Diego, La Jolla, California, United States of America, 3 Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University, Warsaw, Poland, 4 Howard Hughes Medical Institute and Department of Pharmacology, University of California San Diego, La Jolla, California, United States of America The assembly of the ribosome has recently become an interesting target for antibiotics in several bacteria. In this work, we extended an analytical procedure to determine native state fluctuations and contact breaking to investigate the protein stability dependence in the 30S small ribosomal subunit of Thermus thermophilus. We determined the causal influence of the presence and absence of proteins in the 30S complex on the binding free energies of other proteins. The predicted dependencies are in overall agreement with the experimentally determined assembly map for another organism, Escherichia coli. We found that the causal influences result from two distinct mechanisms: one is pure internal energy change, the other originates from the entropy change. We discuss the implications on how to target the ribosomal assembly most effectively by suggesting six proteins as targets for mutations or other hindering of their binding. Our results show that by blocking one out of this set of proteins, the association of other proteins is eventually reduced, thus reducing the translation efficiency even more. We could additionally determine the binding dependency of THX—a peptide not present in the ribosome of E. coli—and suggest its assembly path. Citation: Hamacher K, Trylska J, McCammon JA (2006) De