טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentCohen Liad
SubjectA Geometric Based Approach to Identify Interface
Similarities among DNA and RNA Binding Proteins
DepartmentDepartment of Biology
Supervisor Professor Yael Mandel-Gutfreun
Full Thesis textFull thesis text - English Version


Abstract

DNA binding proteins (DBPs) and RNA binding proteins (RBPs) play a central role in gene regulation pathways in eukaryotes and prokaryotes cells. DBPs are proteins that bind to DNA and act as both activators and repressors of gene expression. RBPs are proteins that bind to RNA molecules. RBPs are involved in post transcription regulation, including splicing of mRNA, polyadenylation, stabilization, localization and translation. Proteins which bind DNA or RNA are often considered and studied independently of one another. However, recent studies have demonstrated that there is a cross talk between the different processes of the gene expression pathway. It has been proposed that this cross talk may be mediated by DNA and RNA binding proteins, possibly possessing dual nucleic acid binding interfaces.

It is well established that the three dimensional structure provides important clues for understanding the function and evolutionary roles of proteins.  Important information can be derived from the protein interface, which is the region of the protein that interacts with other cellular partners. Many computational methods to compare protein structures and protein sequences were developed over the years, yet there is no efficient computational method to evaluate interface similarity. In this study, we employ a new geometry based method that was recently developed in Mandel-Gutfreund lab for efficient comparison of protein surfaces and interfaces, called "PatchBag".  We apply PatchBag to a non-redundant set of DBPs and RBPs in order to search for similarities among DNA and RNA binding interfaces among non-homologous proteins. Using this approach, we revealed unexpected common geometric properties between interfaces that bind DNA and RNA, independent of their electrostatic similarities. We have further constructed an interface similarity network (ISN) to identify the interfaces with high similarities to both DNA and RNA, in search for interfaces which may have a novel role in binding both DNA and RNA partners, possibly granting the protein a dual binding activity. We propose that the proteins detected as hubs in the network may be involved in the cross talk between different regulatory processes in the cell, specifically transcriptional and post-transcriptional regulation.