具有抗癌活性的伴孢晶体蛋白研究进展

田 凌 林 毅

摘要伴孢晶体蛋白是苏云金芽孢杆菌等少数芽孢杆菌在形成芽孢的同时形成的碱溶性蛋白晶体,它对约200种昆虫尤其是鳞翅目的幼虫有杀伤作用,最近人们发现某些菌株的伴孢晶体蛋白存在抗癌活性。概述了伴孢晶体的一般性结构,着重对PS2(Parasporin-2)的抗癌的分子机制进行了深入地剖析,并就研究中存在的问题和发展趋势进行了讨论。

关键词苏云金芽胞杆菌;伴孢晶体;结构;功能;抗癌机理;存在问题

中图分类号 Q516.04 文献标识码A文章编号 1007-5739(2010)09-0027-02

ProgressonaParasporalProteinwithAnticancerActivity

TIAN LingLIN Yi *

(Department of Bioengineering and Biotechnology,Huaqiao University,Xiamen Fujian 361021)

AbstractParasporin(PS) is a collection of genealogically heterogeneous crystal(Cry) proteins synthesized in Bacillus thuringiensis,which is generally known as a valuable source of insecticidal toxins. However,scientists have identified a crystal protein that is non-insecticidal and non-hemolytic but has strong cytocidal activity against various human cancer cells in the recent decade.In this essay,the general structures of the 4 parasporins were summarized respectively,including their physical properties and biological functions. In particular,the 3-dimensional fine structure of the PS2 with deep analysis of the molecular mechanism of anticancer activity was depicted. The problems and prospects about the parasporin were proposed,discussed and commented in this review.

Key wordsBacillus thuringiensis;parasporin;structure;function;anticancer mechanism;existing problems

苏云金芽胞杆菌(Bacillus thuringiensis,简称Bt)是一种革兰氏阳性细菌,于1901年在日本蚕的患病幼体中首次分离得到[1]。在芽胞形成的过程中伴有蛋白晶体的形成,称为伴孢晶体。伴孢晶体是毒杀昆虫的主要活性物质,并在芽胞形成期合成并累积而成。当芽胞成熟以后,细胞自溶,释放出芽胞和伴孢晶体。后者在昆虫中肠内溶解转化成δ-内毒素(也称晶体蛋白,Cry),并与特异性受体高亲和性地结合,快速而不可逆地插入细胞质膜,形成孔或病灶,通过胶体渗透裂解将细胞膨胀并裂解,最后导致昆虫因败血症死亡[2-3]。

随着Bt研究的快速发展,每年都有新的菌株和毒素被鉴定出来,其杀虫谱也越来越宽广[4],同时人们在自然环境中也发现了能产生不具有杀虫活性Cry蛋白的Bt菌株[5-8]。人们对此现象进行了广泛且深入的研究,最后发现这种独特的蛋白能够进攻人类的癌细胞[9]以及会引起人类疾病的原生动物[10]。

1伴孢晶体的结构与功……