2016.10.31. Phase Separation in Biology; A Dominant Role for IDPs
题 目: Phase Separation in Biology; A Dominant Role for IDPs
报告人: Prof. Richard W. Kriwacki
Department of Structural Biology, St. Jude Children's ResearchHospital;
Department of Molecular Sciences, The University ofTennessee
时 间: 2016年10月31日10:00-11:00
地 点: 北京大学化学与分子工程学院A717
主持人: 刘志荣 教授
Macromolecules are partitioned within eukaryotic cells into membrane-bounded compartments and, within these, some are further organized into non-membrane-bounded structures termed membrane-less organelles. These latter structures are comprised of heterogeneous mixtures of proteins, often with intrinsically disordered regions (IDRs), and nucleic acids that assemble through liquid-liquid phase separation, a process similar to polymer condensation. Membrane-less organelles are dynamic structures maintained through transient multivalent interactions that mediate diverse biological processes, many involved in RNA metabolism. The dynamics and structural heterogeneity of IDRs are critical for the dynamic features of proteins within membrane-less organelles. These structures rapidly exchange components with the cellular milieu and their properties are readily altered in response to environmental cues, often implicating membrane-less organelles in responses to stress signaling. We will discuss: (1) the functional roles of membrane-less organelles, (2) unifying structural and mechanistic principles that underlie their assembly and disassembly, and (3) established and emerging methods used in structural investigations of membrane-less organelles. The nucleolus, and its constituent proteins and nucleic acids, will be use to illustrate many of these points.
Richard W. Kriwacki received his Ph.D. from Yale University in 1993. Now he is a member of the department of structural biology, St. Jude Children's Research Hospital and the Adjunct Professor in the department of molecular sciences, the University of Tennessee.
His laboratory seeks to understand the molecular basis of regulation of cell division and apoptosis, with special emphasis on the role of tumor suppressor proteins in these vital biological processes. They apply structural biology and biophysical techniques (NMR spectroscopy, x-ray crystallography, calorimetry, AUC, etc.), as well as biochemical and cell biological methods, to study the details of biomolecular mechanisms from the test tube to cells. Of particular interest is the role of intrinsic protein flexibility in regulatory mechanisms. A new and exciting direction is NMR-based drug discovery against disordered/dynamic proteins.