中国科学技术大学生命科学学院金腾川课题组和加拿大滑铁卢大学Michael Palmer课题组合作，利用X晶体衍射技术首次解析B型链球菌成孔蛋白CAMP因子的晶体结构，并揭示了该毒力因子行使生物学功能的分子机制。研究成果以“Crystal structure of the Streptococcus agalactiae CAMP factor provides insights into its membrane-permeabilizing activity”为题，于6月8日在线发表于Journal of Biological Chemistry杂志。
Streptococcus agalactiae is an important human opportunistic pathogen that can cause serious health problems, particularly among newborns and older individuals. S. agalactiae contains the CAMP factor, a pore-forming toxin first identified in this bacterium. The CAMP reaction is based on the co-hemolytic activity of the CAMP factor and is commonly used to identify S. agalactiae in the clinic. Closely related proteins are present also in other Gram-positive pathogens. Although the CAMP toxin has been discovered more than a half century ago, no structure from this toxin family has been reported, and the mechanism of action of this toxin remains unclear. Here, we report the first structure of this toxin family, revealing a structural fold composed of 5+3 helix bundles. Further analysis by protein truncation and site-directed mutagenesis indicated that the N-terminal 5 helix bundle is responsible for membrane permeabilization, whereas the C-terminal 3 helix bundle is likely responsible for host receptor binding. Interestingly, the C-terminal domain inhibited the activity of both full-length toxin and its N-terminal domain. Moreover, we observed that the linker region is highly conserved and has a conserved DLxxxDxAT sequence motif. Structurally, this linker region extensively interacted with both terminal CAMP factor domains, and mutagenesis disclosed that the conserved sequence motif is required for CAMP factor’s co-hemolytic activity. In conclusion, our results reveal a unique structure of this bacterial toxin and help clarify the molecular mechanism of its co-hemolytic activity.