Structural basis of actin monomer re-charging by cyclase-associated protein

被引：60

作者：

Kotila, Tommi ^{[1
]}

Kogan, Konstantin ^{[1
]}

Enkavi, Giray ^{[2
]}

Guo, Siyang ^{[3
]}

Vattulainen, Ilpo ^{[2
,4
]}

Goode, Bruce L. ^{[3
]}

Lappalainen, Pekka ^{[1
]}

机构：

[1] Univ Helsinki, Inst Biotechnol, Helsinki 00014, Finland

[2] Univ Helsinki, Dept Phys, Helsinki 00014, Finland

[3] Brandeis Univ, Dept Biol, Waltham, MA 02453 USA

[4] Tampere Univ Technol, Lab Phys, FIN-33101 Tampere, Finland

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

芬兰科学院; 欧洲研究理事会;

关键词：

MOLECULAR-DYNAMICS; ARP2/3; COMPLEX; IN-VIVO; NUCLEOTIDE EXCHANGE; FILAMENT TURNOVER; CRYSTAL-STRUCTURE; SRV2/CYCLASE-ASSOCIATED PROTEIN; SRV2/CAP COMPLEX; CAPPING PROTEIN; CELL POLARITY;

D O I：

10.1038/s41467-018-04231-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Actin polymerization powers key cellular processes, including motility, morphogenesis, and endocytosis. The actin turnover cycle depends critically on "re-charging" of ADP-actin monomers with ATP, but whether this reaction requires dedicated proteins in cells, and the underlying mechanism, have remained elusive. Here we report that nucleotide exchange catalyzed by the ubiquitous cytoskeletal regulator cyclase-associated protein (CAP) is critical for actin-based processes in vivo. We determine the structure of the CAP-actin complex, which reveals that nucleotide exchange occurs in a compact, sandwich-like complex formed between the dimeric actin-binding domain of CAP and two ADP-actin monomers. In the crystal structure, the C-terminal tail of CAP associates with the nucleotide-sensing region of actin, and this interaction is required for rapid re-charging of actin by both yeast and mammalian CAPs. These data uncover the conserved structural basis and biological role of protein-catalyzed re-charging of actin monomers.

引用

页数：12

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