Sharma S K, Fu F N, Singh B R
Department of Chemistry and Biochemistry, University of Massachusetts Dartmouth, North Dartmouth 02747, USA.
J Protein Chem. 1999 Jan;18(1):29-38. doi: 10.1023/a:1020691215056.
Clostridium botulinum causes the food poisoning disease botulism by producing botulinum neurotoxin, the most potent toxin known. The neurotoxin is produced along with a group of neurotoxin-associated proteins, or NAPs, which protect it from the low pH and proteases of the gastrointestinal tract. Recently, we isolated one of the major components of NAPs, a 33-kDa hemagglutinin (Hn-33) [Fu et al. (1998), J. Protein Chem. 17, 53-60]. In this study, we present molecular properties of Hn-33 derived from several biochemical and biophysical techniques. Hn-33 in pure form requires a 66-fold lower concentration of sugar inhibition of its hemagglutination activity than in its complexed form with the neurotoxin and other NAPs. However, its protease resistance is not affected by sugar binding. Based on FT-IR and circular dichroism (CD) analysis, Hn-33 is a predominantly beta-sheet protein (74-77%). Hn-33 analysis by laser desorption mass spectrometry and size exclusion column chromatography reveals that it exists predominantly in a dimeric form in the aqueous solution. Even a very low concentration of SDS (0.05%) irreversibly destroyed the biological activity of Hn-33 by changing its secondary structure as revealed by far-UV CD analysis.
肉毒梭菌通过产生肉毒杆菌神经毒素引发食物中毒疾病肉毒中毒,肉毒杆菌神经毒素是已知毒性最强的毒素。神经毒素与一组神经毒素相关蛋白(NAPs)一起产生,这些蛋白可保护它免受胃肠道低pH值和蛋白酶的影响。最近,我们分离出了NAPs的主要成分之一,一种33 kDa的血凝素(Hn-33)[傅等人(1998年),《蛋白质化学杂志》17卷,53 - 60页]。在本研究中,我们展示了通过多种生化和生物物理技术获得的Hn-33的分子特性。与神经毒素和其他NAPs复合形式相比,纯形式的Hn-33对其血凝活性的糖抑制浓度要低66倍。然而,其蛋白酶抗性不受糖结合的影响。基于傅里叶变换红外光谱(FT-IR)和圆二色性(CD)分析,Hn-33主要是一种β-折叠蛋白(74 - 77%)。通过激光解吸质谱和尺寸排阻柱色谱对Hn-33进行分析表明,它在水溶液中主要以二聚体形式存在。如远紫外CD分析所示,即使是非常低浓度的十二烷基硫酸钠(SDS,0.05%)也会通过改变其二级结构不可逆地破坏Hn-33的生物活性。