[대학원 생명과학과 세미나 안내]
연사 : 고준석 교수(서울대학교 생명과학부)
연제 : Intrinsically disordered regions in macromolecular assemblies
일시 : 2018년 11월 16일 (금) 오후 5시
장소 : 하나과학관 A동 B131호
초청교수 : 안지훈 교수
Abstract
Diverse cellular activities are regulated by multi-component macromolecular assemblies. A remarkable feature of many such assemblies is that their protein subunits contain long intrinsically disordered regions (IDRs) dynamically interconverting among multiple conformational states. Despite the abundance of IDRs in the eukaryotic proteome and their strong association with many pathological conditions, it remains elusive how they contribute to the functions of the macromolecular complexes at the molecular level. A representative system for such a problem is the Nuclear Pore Complex (NPC) that mediates molecular transport between the nucleus and the cytoplasm in eukaryotic cells. We characterized biophysical and structural features of the two main sub-complexes of the NPC and the interaction of each sub-complex with transport factors (cargo carriers). Our quantitative characterization demonstrates that these sub-complexes are assembled from weak and dynamic interactions among their building blocks (collectively termed nucleoporins or Nups). Remarkably, binding of a transport factor to an IDR present in each sub-complex allosterically modulates the Nup interaction network and the conformational state of the sub-complex. We propose that allosteric modulation of Nup assemblies by transport factors is critical for the NPC to regulate its conformation in response to various transport demands as well as for NPC biogenesis. The concept of IDR-mediated allostery and the quantitative methods developed in this study should be broadly applicable to other biological systems such as the eukaryotic transcriptional machinery.