4K42

Crystal structure of actin in complex with synthetic AplC tail analogue SF01 [(3R,4S,5R,6S,10R,11R,12R)-11-(acetyloxy)-1-(benzyloxy)-14-[formyl(methyl)amino]-5-hydroxy-4,6,10,12-tetramethyl-9-oxotetradecan-3-yl propanoate]

4K42 の概要

• エントリーDOI: 10.2210/pdb4k42/pdb
• 関連するPDBエントリー: 1QZ5 4K41 4K43
• 分子名称: Actin, alpha skeletal muscle, CALCIUM ION, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: cell motility, gelsolin, contractile protein
• 由来する生物種: Oryctolagus cuniculus (European rabbit,Japanese white rabbit,domestic rabbit,rabbits)
• 細胞内の位置: Cytoplasm, cytoskeleton: P68135
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 171630.56

構造登録者

Pereira, J.H.,Petchprayoon, C.,Moriarty, N.W.,Fink, S.J.,Cecere, G.,Paterson, I.,Adams, P.D.,Marriott, G. (登録日: 2013-04-11, 公開日: 2014-10-01, 最終更新日: 2024-02-28)

主引用文献

Pereira, J.H.,Petchprayoon, C.,Hoepker, A.C.,Moriarty, N.W.,Fink, S.J.,Cecere, G.,Paterson, I.,Adams, P.D.,Marriott, G.
Structural and biochemical studies of actin in complex with synthetic macrolide tail analogues.
Chemmedchem, 9:2286-2293, 2014

PubMed Abstract: The actin filament-binding and filament-severing activities of the aplyronine, kabiramide, and reidispongiolide families of marine macrolides are located within the hydrophobic tail region of the molecule. Two synthetic tail analogues of aplyronine C (SF-01 and GC-04) are shown to bind to G-actin with dissociation constants of (285±33) and (132±13) nM, respectively. The crystal structures of actin complexes with GC-04, SF-01, and kabiramide C reveal a conserved mode of tail binding within the cleft that forms between subdomains (SD) 1 and 3. Our studies support the view that filament severing is brought about by specific binding of the tail region to the SD1/SD3 cleft on the upper protomer, which displaces loop-D from the lower protomer on the same half-filament. With previous studies showing that the GC-04 analogue can sever actin filaments, it is argued that the shorter complex lifetime of tail analogues with F-actin would make them more effective at severing filaments compared with plasma gelsolin. Structure-based analyses are used to suggest more reactive or targetable forms of GC-04 and SF-01, which may serve to boost the capacity of the serum actin scavenging system, to generate antibody conjugates against tumor cell antigens, and to decrease sputum viscosity in children with cystic fibrosis.

PubMed: 25047814
DOI: 10.1002/cmdc.201402150

実験手法

X-RAY DIFFRACTION (2.9 Å)