Tuesday, 27 September 11:00am – 12:00pm

This seminar will be delivered in Chemistry Lecture Theatre 4 and Online Zoom. Please email chemistry.researchsupport@sydney.edu.au for zoom link and password.

Speaker: Prof. Peter Wright; The Scripps Research Institute

Host: Prof. Anthony Masters

Title: Promiscuous liaisons: role of disorder and dynamics in protein function and dysfunction

Abstract: For many decades, a fundamental dogma of molecular and structural biology held that the function of a protein is closely linked to its three-dimensional structure. However, the advent of genome scale sequencing revealed that a significant proportion of gene sequences code for proteins that are entirely unstructured or contain long disordered regions. Such intrinsically disordered proteins (IDPs) are highly abundant in the human proteome and are strongly associated with numerous devastating diseases, including cancers, age-related neurodegenerative disorders (such as Alzheimer’s and Parkinson’s diseases), diabetes, cardiovascular diseases, and infectious diseases. IDPs mediate critical regulatory functions in the cell, including transcription, translation, the cell cycle, and numerous signal transduction events. The lack of stable globular structure confers numerous functional advantages on IDPs, allowing them to exert an exquisite level of control over cellular signaling and cellular organization. IDPs frequently function as central hubs in dynamic regulatory networks, where their propensity for posttranslational modifications, their complex binding and dissociation kinetics, and their ability to interact with multiple target proteins makes them well adapted for precise transduction of cellular signals. IDPs frequently contain multivalent interaction motifs that enable allosteric interactions and generate unidirectional molecular switches. Many viruses hijack their host cells by making extremely effective use of intrinsic disorder to mimic key cellular regulatory proteins that are themselves intrinsically disordered. The unique molecular characteristics of IDPs that underly their diverse biological functions will be illustrated with reference to a molecular switch that controls the response to oxygen stress, mechanisms of regulation of the tumor suppressor p53, and the mechanism by which a human T cell leukemia virus protein dysregulates hematopoiesis.