Event
Special Bioengineering Seminar: Philip Kim
Wednesday, February 27, 2008
2:00 p.m.-3:00 p.m.
0408 Animal Science/Agriculture Engineering Bldg.
Professor Yang Tao
(301) 405-1189
ytao@umd.edu
Jumping scales: How 3D structures and molecular genetics meet in protein networks
Presented by Philip Kim
Department of Molecular Biophysics & Biochemistry
Yale University
Protein interaction networks form the central layer of a systems-level description of the cell. While most studies of protein networks operate on a high level of abstraction, neglecting structural and chemical aspects of each interaction, I will describe our approach of characterizing interactions by using atomic-resolution information from three-dimensional protein structures. We find that some previously recognized relationships between network topology and genomic features (e.g., hubs tending to be essential proteins) are actually more reflective of a structural quantity, the number of distinct binding interfaces. Subdividing hubs with respect to this quantity provides insight into their evolutionary rate and indicates that additional mechanisms of network growth are active in evolution.
Furthermore, I will provide an overview of a major international collaborative effort that aims to resolve interactions involved in signaling pathways. These tend to involve intrinsically disordered regions are hence complementary to the structured interactions studied by the above approach. Our approach combines modern experimental screening techniques with a novel integrated analysis pipeline. The former screens measure binding specificities with hitherto unachievable accuracy and the analysis pipeline maximizes prediction accuracy by integrating a variety of genomic and proteomic features.
Lastly, I will present a study that examined the relationship between genetic signatures of adaptive evolution and proteomic properties, such as the location of sites in protein networks and structures. Due to recent advances in genotyping and sequencing technology, human genetic variation and adaptive evolution in the primate lineage have become a major research focus. We find a striking tendency of proteins that have been subject to adaptive evolution (as compared to the chimpanzee) to be located at the periphery of the interaction network. We also find that the fixation of large-scale copy number variants into segmental duplications also preferentially occurs at the network periphery, bolstering our argument for selection at periphery. This suggests that the observed preferential selection at the network periphery may be due to an increase of adaptive events on the cellular periphery responding to changing environments.
