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来自姬蛙属幼蛙腺体皮肤分泌物的含二硫键肽:结构、活性及进化趋势

Disulfide-containing peptides from the glandular skin secretions of froglets of the genus Crinia: structure, activity and evolutionary trends.

作者信息

Jackway Rebecca J, Pukala Tara L, Maselli Vita M, Musgrave Ian F, Bowie John H, Liu Yanqin, Surinya-Johnson Katharina H, Donnellan Stephen C, Doyle Jason R, Llewellyn Lyndon E, Tyler Michael J

机构信息

Department of Chemistry, The University of Adelaide, 5005, South Australia, Australia.

出版信息

Regul Pept. 2008 Nov 29;151(1-3):80-7. doi: 10.1016/j.regpep.2008.06.004. Epub 2008 Jun 17.

DOI:10.1016/j.regpep.2008.06.004
PMID:18601958
Abstract

The skin secretions of Crinia signifera, C. riparia and C. deserticola contain bioactive disulfide-containing peptides. Signiferin 1 (RLCIPYIIPC-OH) from C. signifera and C. deserticola) contracts smooth muscle at a concentration of 10(-9) M, and effects proliferation of lymphocytes at 10(-6) M. In contrast, riparin 1.1 (RLCIPVIFC-OH) and riparin 1.2 (FLPPCAYKGTC-OH) from C. riparia show lymphocyte activity but do not contract smooth muscle. The lymphocyte and smooth muscle activities involve CCK2R. 3D structures of signiferin 1 and riparin 1.1 have been established using 2D NMR methods: these studies show significant differences in the shapes of the disulfide rings and with the orientations of the N-terminal residues. cDNA cloning establishes that the pre sections of the precursor pre-pro-riparin 1.4-1.6 peptides are different from the conserved pre regions of disulfide-containing antimicrobial peptides from species of the genus Rana found in the northern hemisphere and caerin antimicrobial peptides isolated from Australian tree frogs of the genus Litoria. This suggests that (i) either that riparins 1 have converged to similar structure and function to the ranid and hyloid prepropeptides which were lost initially from the myobatrachid lineage, or (ii) the prepropeptides in all three groups were derived from a single ancestral form that has remained relatively conserved in the hyloid and ranoid lineages but has undergone substantial divergent evolution in the myobatrachids.

摘要

铃蟾(Crinia signifera)、河栖铃蟾(C. riparia)和荒漠铃蟾(C. deserticola)的皮肤分泌物含有具有生物活性的含二硫键肽。来自铃蟾和荒漠铃蟾的信号肽1(RLCIPYIIPC - OH)在浓度为10⁻⁹ M时可使平滑肌收缩,在10⁻⁶ M时影响淋巴细胞增殖。相比之下,来自河栖铃蟾的河栖肽1.1(RLCIPVIFC - OH)和河栖肽1.2(FLPPCAYKGTC - OH)具有淋巴细胞活性,但不使平滑肌收缩。淋巴细胞和平滑肌活性涉及CCK2R。已使用二维核磁共振方法确定了信号肽1和河栖肽1.1的三维结构:这些研究表明二硫键环的形状以及N端残基的方向存在显著差异。cDNA克隆表明,前体前 - 原河栖肽1.4 - 1.6肽的前区与在北半球发现的林蛙属含二硫键抗菌肽的保守前区以及从澳大利亚雨滨蛙属树蛙分离的凯林抗菌肽不同。这表明:(i)要么河栖肽1已经趋同于最初从姬蛙科谱系中丢失的蛙科和雨蛙科前原肽的相似结构和功能,要么(ii)所有这三组的前原肽都源自单一的祖先形式,该形式在雨蛙科和蛙科谱系中相对保守,但在姬蛙科中经历了大量的趋异进化。

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