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皮肤肽抗生素家族——皮肤防御素B的结构、合成及分子克隆

Structure, synthesis, and molecular cloning of dermaseptins B, a family of skin peptide antibiotics.

作者信息

Charpentier S, Amiche M, Mester J, Vouille V, Le Caer J P, Nicolas P, Delfour A

机构信息

Laboratoire de Bioactivation des Peptides, Institut Jacques Monod, 2 Place Jussieu, 75251 Paris Cedex 05, France.

出版信息

J Biol Chem. 1998 Jun 12;273(24):14690-7. doi: 10.1074/jbc.273.24.14690.

DOI:10.1074/jbc.273.24.14690
PMID:9614066
Abstract

Analysis of antimicrobial activities that are present in the skin secretions of the South American frog Phyllomedusa bicolor revealed six polycationic (lysine-rich) and amphipathic alpha-helical peptides, 24-33 residues long, termed dermaseptins B1 to B6, respectively. Prepro-dermaseptins B all contain an almost identical signal peptide, which is followed by a conserved acidic propiece, a processing signal Lys-Arg, and a dermaseptin progenitor sequence. The 22-residue signal peptide plus the first 3 residues of the acidic propiece are encoded by conserved nucleotides encompassed by the first coding exon of the dermaseptin genes. The 25-residue amino-terminal region of prepro-dermaseptins B shares 50% identity with the corresponding region of precursors for D-amino acid containing opioid peptides or for antimicrobial peptides originating from the skin of distantly related frog species. The remarkable similarity found between prepro-proteins that encode end products with strikingly different sequences, conformations, biological activities and modes of action suggests that the corresponding genes have evolved through dissemination of a conserved "secretory cassette" exon.

摘要

对南美洲双色叶泡蛙皮肤分泌物中的抗菌活性进行分析后发现了六种多阳离子(富含赖氨酸)且具有两亲性α螺旋的肽,长度为24 - 33个残基,分别命名为皮肤防御素B1至B6。前体皮肤防御素B均含有几乎相同的信号肽,其后是一个保守的酸性前肽、一个加工信号Lys-Arg以及一个皮肤防御素前体序列。22个残基的信号肽加上酸性前肽的前3个残基由皮肤防御素基因第一个编码外显子所包含的保守核苷酸编码。前体皮肤防御素B的25个残基氨基末端区域与含D-氨基酸的阿片样肽或源自远缘蛙类皮肤的抗菌肽前体的相应区域有50%的同源性。在编码具有显著不同序列、构象、生物活性和作用方式的终产物的前体蛋白之间发现的显著相似性表明,相应的基因是通过一个保守的“分泌盒”外显子的传播而进化的。

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