O'Neal Claire J, Jobling Michael G, Holmes Randall K, Hol Wim G J
Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
Science. 2005 Aug 12;309(5737):1093-6. doi: 10.1126/science.1113398.
The Vibrio cholerae bacterium causes devastating diarrhea when it infects the human intestine. The key event is adenosine diphosphate (ADP)-ribosylation of the human signaling protein GSalpha, catalyzed by the cholera toxin A1 subunit (CTA1). This reaction is allosterically activated by human ADP-ribosylation factors (ARFs), a family of essential and ubiquitous G proteins. Crystal structures of a CTA1:ARF6-GTP (guanosine triphosphate) complex reveal that binding of the human activator elicits dramatic changes in CTA1 loop regions that allow nicotinamide adenine dinucleotide (NAD+) to bind to the active site. The extensive toxin:ARF-GTP interface surface mimics ARF-GTP recognition of normal cellular protein partners, which suggests that the toxin has evolved to exploit promiscuous binding properties of ARFs.
霍乱弧菌感染人类肠道时会引发严重腹泻。关键事件是霍乱毒素A1亚基（CTA1）催化人类信号蛋白GSα的二磷酸腺苷（ADP）核糖基化。该反应由人类ADP核糖基化因子（ARF）别构激活，ARF是一类重要且普遍存在的G蛋白家族。CTA1:ARF6 - 三磷酸鸟苷（GTP）复合物的晶体结构表明，人类激活剂的结合会引发CTA1环区域的显著变化，从而使烟酰胺腺嘌呤二核苷酸（NAD +）能够结合到活性位点。广泛的毒素:ARF - GTP界面表面模拟了ARF - GTP对正常细胞蛋白伙伴的识别，这表明该毒素已经进化到利用ARF的混杂结合特性。
