Allostery and molecular stripping mechanism in profilin regulated actin filament growth

被引:1
作者
Zhang, Weiwei [1 ,2 ]
Cao, Yi [1 ,2 ,3 ]
Li, Wenfei [1 ,2 ,3 ]
Wang, Wei [1 ,2 ]
机构
[1] Nanjing Univ, Dept Phys, Natl Lab Solid State Microstruct, Nanjing 210093, Peoples R China
[2] Nanjing Univ, Collaborat Innovat Ctr Adv Microstruct, Nanjing 210093, Peoples R China
[3] Univ Chinese Acad Sci, Wenzhou Inst, Wenzhou 325000, Zhejiang, Peoples R China
来源
NEW JOURNAL OF PHYSICS | 2021年 / 23卷 / 12期
基金
中国国家自然科学基金;
关键词
actin filament; profilin; allostery; molecular dynamics; polarized growth; STRUCTURAL BASIS; ADENYLATE KINASE; BARBED END; DYNAMICS SIMULATIONS; MONOMERIC ACTIN; PROTEIN; NUCLEOTIDE; POLYMERIZATION; ELONGATION; LANDSCAPE;
D O I
10.1088/1367-2630/ac3b2d
中图分类号
O4 [物理学];
学科分类号
0702 ;
摘要
Profilin is an actin-sequestering protein and plays key role in regulating the polarized growth of actin filament. Binding of profilin to monomeric actin (G-actin) allows continuous elongation at the barbed end (BE), but not the pointed end, of filament. How G-actin exchanges between the profilin-sequestered state and the filament state (F-actin) to support the BE elongation is not well understood. Here, we investigate the involved molecular mechanism by constructing a multi-basin energy landscape model and performing molecular simulations. We showed that the actin exchanging occurs by forming a ternary complex. The interactions arising from the BE binding drive the conformational change of the attached G-actin in the ternary complex from twist conformation to more flatten conformation without involving the change of nucleotide state, which in turn destabilizes the actin-profilin interface and promotes the profilin stripping event through allosteric coupling. We also showed that attachment of free profilin to the BE induces conformational change of the BE actin and facilitates its stripping from the filament. These results suggest a molecular stripping mechanism of the polarized actin filament growth dynamics controlled by the concentrations of the actin-profilin dimer and the free profilin, in which the allosteric feature of the monomeric actin plays crucial role.
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页数:14
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