Seminar

2021년 2학기 마지막 생명과학과 열린세미나 연사님은 서울대학교 생명과학부 고준석 교수님입니다.

고준석 교수님은, 세포내에서 일어나는 다양한 생명현상에 관련된 복합체들에 대한 생물리화학적 특성을 연구 하고 계십니다.

특히 복합체를 구성하는 서브유닛들이 결합하면서 어떤 구조적 변화가 생기는지, 그리고 그 구조적 변화가 어떤 물리화학적 특성을 갖는 구조변화인지를 규명하는 연구로, 이번 세미나에서는 특별히 핵막에 위치하여 세포질과 핵 사이에서 molecular transport 를 담당하는 NPC 내의 구조 변화에 대해 소개해 주실 예정입니다.  

- 온라인(실시간 스트리밍) 접속링크(ZOOM)

https://us02web.zoom.us/j/3299955127?pwd=WVJkYVlkNEhqUHQxK2MvZDFwejRtUT09
Meeting ID: 329 995 5127
Passcode: 965572

Intrinsically disordered proteins (IDPs) in dynamic cellular processes

Abstract

Prevalent in diverse protein interactomes, intrinsically disordered proteins or regions (IDPs or IDRs) often drive assembly of higher-order macromolecular complexes, using multiple target-binding motifs. Such IDP hubs are suggested to process various cellular signals and coordinate relevant biological processes. However, the mechanism of assembly and functional regulation of IDP hubs remains elusive due to the challenges in dissecting their intricate protein-protein interaction networks. Here we present basic thermodynamic models for the assembly of simple IDP hubs with multiple target proteins, constructing partition functions from fundamental binding parameters. We combined these basic functions to develop advanced thermodynamic models to analyze the assembly of the Nup153 hubs interacting with multiple karyopherin β1 (Kap) molecules, critical components of nucleocytoplasmic transport. The thermodynamic analysis revealed a complex organization of the Kap binding sites within the C-terminal IDR of Nup153 including a high-affinity 1:1 interaction site and a series of low-affinity sites for binding of multiple Kaps with negative cooperativity. The negative cooperativity arises from the overlapping nature of the low-affinity sites where Kap occupies multiple dipeptide motifs. The quantitative dissection culminated in construction of the Nup153 hub ensemble, elucidating how distribution among various Kap-bound states is modulated by Kap concentration and competing nuclear proteins. In particular, the Kap occupancy of the IDR can be fine-tuned by varying the location of competition within the overlapping sites, suggesting coupling of specific nuclear processes to distinct transport activities. In general, our results demonstrate the feasibility and a potential mechanism for manifold regulation of IDP functions by diverse cellular signals.