Oldenburg D J, Storm D R
Department of Pharmacology, University of Washington School of Medicine, Seattle 98195.
Microb Pathog. 1993 Aug;15(2):153-7. doi: 10.1006/mpat.1993.1065.
Bordetella pertussis produces a calmodulin-stimulated adenylyl cyclase that invades animal cells and raises intracellular cAMP levels. The enzyme does not enter animal cells by receptor-mediated endocytosis, but the mechanism for invasion of animal cells has not been defined. We have proposed that the 177 kDa adenylyl cyclase is proteolyzed to a 45 kDa catalytic subunit and one or more polypeptides (invasive factor) that facilitate entry of the catalytic subunit into animal cells. In this study, we report the identification of a sequence of amino acids within the adenylyl cyclase catalytic subunit that is important for entry of the enzyme into eukaryotic cells. A synthetic peptide corresponding to amino acids 313-339 within the catalytic subunit was shown to inhibit invasion of neuroblastoma cells by the adenylyl cyclase. In addition, this peptide inhibited the association of the catalytic subunit with invasive factor. We propose that this domain is a site for interaction between the catalytic subunit and invasive factor.
百日咳博德特氏菌产生一种钙调蛋白刺激的腺苷酸环化酶，该酶可侵入动物细胞并提高细胞内cAMP水平。该酶并非通过受体介导的内吞作用进入动物细胞，但其侵入动物细胞的机制尚未明确。我们曾提出，177 kDa的腺苷酸环化酶被蛋白酶解为一个45 kDa的催化亚基和一种或多种促进催化亚基进入动物细胞的多肽（侵袭因子）。在本研究中，我们报告了腺苷酸环化酶催化亚基内一段对该酶进入真核细胞很重要的氨基酸序列的鉴定结果。一段对应于催化亚基内313 - 339位氨基酸的合成肽被证明可抑制腺苷酸环化酶对神经母细胞瘤细胞的侵袭。此外，该肽还抑制了催化亚基与侵袭因子的结合。我们认为该结构域是催化亚基与侵袭因子之间相互作用的位点。
