Vector Biology Section, Laboratory of Malaria Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA.
Toxins (Basel). 2012 May;4(5):296-322. doi: 10.3390/toxins4050296. Epub 2012 Apr 26.
Bloodsucking arthropods are a rich source of salivary molecules (sialogenins) which inhibit platelet aggregation, neutrophil function and angiogenesis. Here we review the literature on salivary disintegrins and their targets. Disintegrins were first discovered in snake venoms, and were instrumental in our understanding of integrin function and also for the development of anti-thrombotic drugs. In hematophagous animals, most disintegrins described so far have been discovered in the salivary gland of ticks and leeches. A limited number have also been found in hookworms and horseflies, and none identified in mosquitoes or sand flies. The vast majority of salivary disintegrins reported display a RGD motif and were described as platelet aggregation inhibitors, and few others as negative modulator of neutrophil or endothelial cell functions. This notably low number of reported disintegrins is certainly an underestimation of the actual complexity of this family of proteins in hematophagous secretions. Therefore an algorithm was created in order to identify the tripeptide motifs RGD, KGD, VGD, MLD, KTS, RTS, WGD, or RED (flanked by cysteines) in sialogenins deposited in GenBank database. The search included sequences from various blood-sucking animals such as ticks (e.g., Ixodes sp., Argas sp., Rhipicephalus sp., Amblyommasp.), tabanids (e.g., Tabanus sp.), bugs (e.g., Triatoma sp., Rhodnius prolixus), mosquitoes (e.g., Anopheles sp., Aedes sp., Culex sp.), sand flies (e.g., Lutzomyia sp., Phlebotomus sp.), leeches (e.g., Macrobdella sp., Placobdella sp.) and worms (e.g., Ancylostoma sp.). This approach allowed the identification of a remarkably high number of novel putative sialogenins with tripeptide motifs typical of disintegrins (>450 sequences) whose biological activity remains to be verified. This database is accessible online as a hyperlinked worksheet and displays biochemical, taxonomic, and gene ontology aspects for each putative disintegrin. It is also freely available for download (right click with the mouse) at links http://exon.niaid.nih.gov/transcriptome/RGD/RGD-Peps-WEB.xlsx (web version) and http://exon.niaid.nih.gov/transcriptome/RGD/RGD-sialogenins.zip (stand alone version).
吸血节肢动物是唾液分子（唾液分泌素）的丰富来源，这些分子可以抑制血小板聚集、中性粒细胞功能和血管生成。在这里，我们回顾了唾液整合素及其靶标的文献。整合素最初是在蛇毒中发现的，它们对于我们理解整合素的功能以及抗血栓药物的开发都非常重要。在吸血动物中，迄今为止描述的大多数整合素都在蜱和水蛭的唾液腺中发现。在钩虫和马蝇中也发现了少量的整合素，但在蚊子或沙蝇中没有发现。报告的绝大多数唾液整合素都显示出 RGD 基序，被描述为血小板聚集抑制剂，少数作为中性粒细胞或内皮细胞功能的负调节剂。在吸血分泌物中，报告的整合素数量如此之少，肯定是对该蛋白家族实际复杂性的低估。因此，创建了一个算法，以便在 GenBank 数据库中识别唾液分泌素中三肽基序 RGD、KGD、VGD、MLD、KTS、RTS、WGD 或 RED（由半胱氨酸侧翼）。该搜索包括来自各种吸血动物的序列，如蜱（例如，Ixodes sp.、Argas sp.、Rhipicephalus sp.、Amblyommasp.）、虻（例如，Tabanus sp.）、臭虫（例如，Triatoma sp.、Rhodnius prolixus）、蚊子（例如，Anopheles sp.、Aedes sp.、Culex sp.）、沙蝇（例如，Lutzomyia sp.、Phlebotomus sp.）、水蛭（例如，Macrobdella sp.、Placobdella sp.）和蠕虫（例如，Ancylostoma sp.）。这种方法允许鉴定出数量惊人的具有典型整合素三肽基序的新型假定唾液分泌素（>450 个序列），其生物学活性仍有待验证。该数据库可在线访问，作为一个超链接工作表，显示每个假定整合素的生化、分类学和基因本体论方面。也可以通过以下链接以鼠标右键单击的方式自由下载（网络版）和（独立版）：http://exon.niaid.nih.gov/transcriptome/RGD/RGD-Peps-WEB.xlsx 和 http://exon.niaid.nih.gov/transcriptome/RGD/RGD-sialogenins.zip。
