Protein complexes in snake venom

Snake venom contains mixture of bioactive proteins and polypeptides. Most of these proteins and polypeptides exist as monomers, but some of them form complexes in the venom. These complexes exhibit much higher levels of pharmacological activity compared to individual components and play an important role in pathophysiological effects during envenomation. They are formed through covalent and/or non-covalent interactions. The subunits of the complexes are either identical (homodimers) or dissimilar (heterodimers; in some cases subunits belong to different families of proteins). The formation of complexes, at times, eliminates the non-specific binding and enhances the binding to the target molecule. On several occasions, it also leads to recognition of new targets as protein-protein interaction in complexes exposes the critical amino acid residues buried in the monomers. Here, we describe the structure and function of various protein complexes of snake venoms and their role in snake venom toxicity.     

ADAM proteases: ligand processing and modulation of the Notch pathway

ADAM metalloproteases play important roles in development and disease. One of the key functions of ADAMs is the proteolytic processing of Notch receptors and their ligands. ADAM-mediated cleavage of Notch represents the first step in regulated intramembrane proteolysis of the receptor, leading to activation of the Notch pathway. Recent reports indicate that the transmembrane Notch ligands also undergo ADAM-mediated processing in cultured cells and in vivo. The proteolytic processing of Notch ligands modulates the strength and duration of Notch signals, leads to generation of soluble intracellular domains of the ligands, and may support a bi-directional signaling between cells.     

人类ADAM家族成员ADAM23a的克隆

应用与ADAM家族成员高度同源，来自人胎脑的EST（espressed sequence tag)为探针，从人22周胎脑cDNA文库中分离到3．0kb长的cDNA片段，除了C末端缺少91nt外，与ADAM23同源性达100％，编码的蛋白未能形成明显的跨膜区，定名为ADAM23a，在检测中发现，该基因与ADAM23的C末端相同位置的氨基酸序列中，分析其金属蛋白酶功能域(metalloproteinase domain)，不含有结合Zn的活性位点，去整联蛋白功能域（Disintegrin domain)与ADAM部分成员具有同源性，在人16种组织的Northern blot检测，ADAM23a仅在心脏和脑中表达，由于2种cDNA从不同发育时期的胎脑及脑中分离得到，有可能是在发育过程中受到了调节，可能通过去整联蛋白功能域与脑和心脏中的整联蛋白（integrin)相互作用。     

R~(49)A~(50)RGDN~(54)P~(55)突变成I~(49)P~(50)RGDM~(54)P~(55)对华丽蛇毒素活性的影响(英文)

用基因点突变技术将已知具有强抑制血小板凝集作用的去整合蛋白———kistrin的RGD袢区IPRGDMP替换抑制血小板凝集作用较弱的elegantinRGD袢相应部位的RARGDNP,重构一个新的杂合的去整合蛋白,然后,分析该杂合蛋白对血小板凝集的抑制作用。结果表明,重组的杂合去整合蛋白比野生型elegantin具有更强的抑制血小板凝集活性。推测RGD顺序两翼的氨基酸残基在保持去整合蛋白的结构和功能中起重要作用。