Bradykinin-related peptides from Phyllomedusa hypochondrialis azurea:: mass spectrometric structural characterisation and cloning of precursor cDNAs
Bradykinin-related peptides from Phyllomedusa hypochondrialis azurea:: mass spectrometric structural characterisation and cloning of precursor cDNAs
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DOI：
10.1002/rcm.2791
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发表时间：
2006-01-01
影响因子：
2
通讯作者：
McClean, Stephen
中科院分区：
文献类型：
--
作者：
Thompson, Alan Hunter;Bjourson, Anthony John;McClean, Stephen
两栖动物的皮肤分泌物含有大量生物活性化合物，其中许多据了解可起到阻止捕食者吞食的作用。缓激肽尤其在许多两栖动物的皮肤分泌物中组成性表达，介导多种效应，包括痛觉过敏和胃平滑肌收缩。通过运用多种蛋白质组学技术（高效液相色谱（HPLC）分离、基质辅助激光解吸/电离飞行时间质谱（MALDI - TOFMS）以及四极杆飞行时间串联质谱（Q - TOF - MS/MS）），当前的研究在蓝腹叶蛙（Phyllomedusa hypochondrialis azurea）的皮肤分泌物中鉴定出13种缓激肽样肽，包括几种新的C末端延伸异构体（VPPGFTPFRLT、VHypPGFTPFRQT）以及一种新型叶蛙激肽样肽（RPPGFTPFRVY）。对编码这些肽的cDNA序列的鉴定推断出这些肽源自五种不同前体的差异性翻译后加工和修饰。这样的事件强调了两栖动物毒液中肽产生的代谢效率，多种产物可能对来自单一前体的各种捕食者体内的不同受体具有选择性。在本研究中还发现了一种不寻常的修饰，几种缓激肽样肽的第一个脯氨酸残基发生羟脯氨酸化，而非通常靶向的第二个。这种改变可能是由前体加工之前N末端氨基酸的结构组织所介导的。版权所有（c）2006约翰威立父子有限公司
Amphibian skin secretions contain a plethora of bioactive compounds, many of which are understood to act to deter ingestion by predators. Bradykinins in particular are constitutively expressed in many amphibian skin secretions, mediating a variety of effects including hyperalgesia and contraction of gastric smooth muscle. Using a variety of proteomic techniques (high-performance liquid chromatography (HPLC) separation, matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOFMS), and quadrupole time-of-flight tandem mass spectrometry (Q-TOF-MS/MS)) the current study identified 13 bradykinin-like peptides in the skin secretions of Phyllomedusa hypochondrialis azurea, including several new C-terminally extended isoforms (VPPGFTPFRLT, VHypPGFTPFRQT) and a novel phyllokinin-like peptide (RPPGFTPFRVY). Identification of the cDNA sequences encoding these peptides led to the deduction that the peptides were derived from differential post-translational processing and modification of five different precursors. Such an event emphasises the metabolic efficiency of peptide production in amphibian venom, with multiple products perhaps selective to different receptors in a variety of predators generated from a single precursor. An unusual modification was also recognised in the present study, with several bradykinin-like peptides featuring hydroxyprolination of the first proline residue rather than the commonly targeted second. This alteration may be mediated by the structural organisation of N-terminal amino acids prior to precursor processing. Copyright (c) 2006 John Wiley & Sons, Ltd.