Molecular Biology of the Ribonuclease A Gene Superfamily

核糖核酸酶 A 基因超家族的分子生物学

• 批准号: 8156960
• 负责人: HELENE ROSENBERG
• 金额: $ 19.07万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8156960
• 关键词: Genes; Molecular Biology; Pancreatic ribonuclease

Ongoing projects in our laboratory focus primarily on RNase A ribonucleases that promote host defense (the eosinophil ribonucleases, RNases 7 and 8, and leukocyte RNase A-2) with efforts directed toward understanding their biology, evolution and mechanism of antimicrobial action (Moser, Chan et al., in preparation). During this reporting period, we published the results of a study initiated by Dr. Wei Zhao during his sabbatical from Beijing Union College, Beijing, China, that was continued and completed as a result of the substantial efforts of a summer intern, Steven Siegel. In an effort to augment our current understanding of divergent mammalian RNase A ribonuclease sequences, we identified novel RNase 1 genes from four species of squirrel (order Rodentia, family Sciuridae). Squirrel RNase 1 genes encode typical RNase A ribonucleases, each with eight cysteines, a conserved CKXXNTF signature motif, and a canonical His(12)-Lys(41)-His(119) catalytic triad. Two alleles encode Callosciurus prevostii RNase 1, which include a Ser(18)<-->Pro, analogous to the sequence polymorphisms found among the RNase 1 duplications in the genome of Rattus exulans. Interestingly, although the squirrel RNase 1 genes are closely related to one another (77-95% amino acid sequence identity), the cluster as a whole is distinct and divergent from the clusters including RNase 1 genes from other rodent species. We examined the specific sites at which Sciuridae RNase 1s diverge from Muridae/Cricetidae RNase 1s and determined that the divergent sites are located on the external surface, with complete sparing of the catalytic crevice.

我们实验室正在进行的项目主要集中在促进宿主防御的RNase A核糖核酸酶（嗜酸性粒细胞核糖核酸酶，RNase 7和8，以及白细胞RNase A-2），努力了解它们的生物学，进化和抗菌作用机制（Moser， Chan等人，正在准备中）。