Abstract:

The classical structure-to-function paradigm states that the sequence of amino acids in a protein dictates a specific 3D structure that is critical for its function. However, in the past four decades, the awareness of wide occurrence and functional importance of protein regions without stable secondary and tertiary structure, or intrinsically disordered proteins and regions (IDPRs), have challenged this conventional view. Whereas protein dynamics of IDPRs play a central role in description of their behaviour in solution, how do cells leverage the conformational features of IDPRs under various structural and cellular context for physiological functions still remain fully elucidated. In this talk, I will demonstrate how we combine computational sequence analysis and cross-scale experimental characterizations to study IDPR functions at the protein-membrane interface. Specifically, we have discovered protein sequence features that are conserved during evolution for (1) regulation of membrane biophysical properties by an abiotic stress-tolerant protein from tardigrade; (2) control of COPII vesicle size and occupancy in ER-to-Golgi trafficking. Our discoveries highlight the evolutionary selection for protein structural disorder as a solution to complex requirements from cells and environments.