Signaling in the crowded cell

被引:13
作者
Nussinov, Ruth [1 ,2 ]
Tsai, Chung-Jung [1 ]
Jang, Hyunbum [1 ]
机构
[1] NCI, Frederick Natl Lab Canc Res, Lab Canc Immunometab, Computat Struct Biol Sect, Frederick, MD 21701 USA
[2] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel
基金
美国国家卫生研究院;
关键词
RAS ISOFORMS; H-RAS; K-RAS; ALLOSTERIC CONTROL; CHROMATIN; ACTIVATION; ORGANIZATION; MUTATIONS; DYNAMICS; REVEALS;
D O I
10.1016/j.sbi.2021.05.009
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
High-resolution technologies have clarified some of the principles underlying cellular actions. However, understanding how cells receive, communicate, and respond to signals is still challenging. Questions include how efficient regulation of assemblies, which execute cell actions at the nanoscales, transmits productively at micrometer scales, especially considering the crowded environment, and how the cell organization makes it happen. Here, we describe how cells can navigate long-range diffusion-controlled signaling via association/dissociation of spatially proximal entities. Dynamic clusters can span the cell, engaging in most signaling steps. Effective local concentration, allostery, scaffolding, affinities, and the chemical and mechanical properties of the macromolecules and the environment play key roles. Signaling strength and duration matter, for example, deciding if a mutation promotes cancer or developmental syndromes.
引用
收藏
页码:43 / 50
页数:8
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