Sharma Alok, Pohlentz Gottfried, Bobbili Kishore Babu, Jeyaprakash A Arockia, Chandran Thyageshwar, Mormann Michael, Swamy Musti J, Vijayan M
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, Karnataka, India.
Acta Crystallogr D Biol Crystallogr. 2013 Aug;69(Pt 8):1493-503. doi: 10.1107/S0907444913010020. Epub 2013 Jul 18.
The sequence and structure of snake gourd seed lectin (SGSL), a nontoxic homologue of type II ribosome-inactivating proteins (RIPs), have been determined by mass spectrometry and X-ray crystallography, respectively. As in type II RIPs, the molecule consists of a lectin chain made up of two β-trefoil domains. The catalytic chain, which is connected through a disulfide bridge to the lectin chain in type II RIPs, is cleaved into two in SGSL. However, the integrity of the three-dimensional structure of the catalytic component of the molecule is preserved. This is the first time that a three-chain RIP or RIP homologue has been observed. A thorough examination of the sequence and structure of the protein and of its interactions with the bound methyl-α-galactose indicate that the nontoxicity of SGSL results from a combination of changes in the catalytic and the carbohydrate-binding sites. Detailed analyses of the sequences of type II RIPs of known structure and their homologues with unknown structure provide valuable insights into the evolution of this class of proteins. They also indicate some variability in carbohydrate-binding sites, which appears to contribute to the different levels of toxicity exhibited by lectins from various sources.
蛇瓜籽凝集素（SGSL）是II型核糖体失活蛋白（RIPs）的无毒同源物，其序列和结构已分别通过质谱分析和X射线晶体学确定。与II型RIPs一样，该分子由一条由两个β-三叶结构域组成的凝集素链构成。在II型RIPs中通过二硫键与凝集素链相连的催化链，在SGSL中被切割成两段。然而，该分子催化成分的三维结构完整性得以保留。这是首次观察到三链RIP或RIP同源物。对该蛋白质的序列、结构及其与结合的甲基-α-半乳糖的相互作用进行的全面研究表明，SGSL的无毒特性源于催化位点和碳水化合物结合位点的变化组合。对已知结构的II型RIPs及其未知结构的同源物序列进行的详细分析，为这类蛋白质的进化提供了有价值的见解。它们还表明碳水化合物结合位点存在一些变异性，这似乎导致了不同来源凝集素表现出的不同毒性水平。
