Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
Molecular Dynamics Studies of HTLV-1 Rex Responsive Element Aptamer Recognition
Rex protein recognition of the Rex responsive element (RxRE) is a critical step in the retroviral lifecycle of human T-cell leukemia type 1. The Rex peptide is known to have a higher binding affinity for the synthetically derived RexRE aptamer (RxREA) than the wild-type RNA (Jiang 1999). The purpose of this study is to better understand the roles that arginine-rich motifs and the role of water Rex recognition of RxRE aptamer. Explicit water molecular dynamics simulations of wild-type Rex peptide bound to the RxREA have been simulated from all NMR structures. Simulations of two mutant peptides, R7K and R13K, that combined exhibit a 30-fold decrease in binding affinity to the RxREA were also undertaken. The presence of hydrogen bonds between protein and RNA has been compared across multiple models, and sites of high water density have been examined. Key water molecules have been found to bridge R13 and R7 to the RNA. Upon mutation to lysine, some of those water-molecule binding sites have been lost. The inherent flexibility of the wild-type S-shaped peptide allows the mutant peptides to adapt easily and compensate for the loss of water molecules. Comparing this system to the role of water in other arginine rich peptide-RNA complexes will lead to a better understanding of peptide-RNA recognition in general.
This research has been supported by NSF MRI (CHE-1229354) and Research Corporation (CC6553).
Jiang, F., Gorin, A., Hu, W., Majumdar, A. Baskerville, S., Xu, W., Ellington, A. and Patel, D. J. (1999). Anchoring an extended HTLV-1 Rex peptide within an RNA major groove containing junctional base triples. Structure 7, 1461-1472.
Zachary J. Fallon
Department of Chemistry