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蜂毒素的应用与演变:一种典型的膜活性肽。

Applications and evolution of melittin, the quintessential membrane active peptide.

机构信息

University of Texas Health Science Center at Houston, Department of Microbiology and Molecular Genetics, Houston, TX, USA.

Tulane University School of Medicine, Department of Biochemistry and Molecular Biology, New Orleans, LA, USA.

出版信息

Biochem Pharmacol. 2021 Nov;193:114769. doi: 10.1016/j.bcp.2021.114769. Epub 2021 Sep 17.

DOI:10.1016/j.bcp.2021.114769
PMID:34543656
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9235364/
Abstract

Melittin, the main venom component of the European Honeybee, is a cationic linear peptide-amide of 26 amino acid residues with the sequence: GIGAVLKVLTTGLPALISWIKRKRQQ-NH. Melittin binds to lipid bilayer membranes, folds into amphipathic α-helical secondary structure and disrupts the permeability barrier. Since melittin was first described, a remarkable array of activities and potential applications in biology and medicine have been described. Melittin is also a favorite model system for biophysicists to study the structure, folding and function of peptides and proteins in membranes. Melittin has also been used as a template for the evolution of new activities in membranes. Here we overview the rich history of scientific research into the many activities of melittin and outline exciting future applications.

摘要

蜂毒素是欧洲蜜蜂毒液的主要成分,是一种 26 个氨基酸残基的阳离子线性肽酰胺,序列为:GIGAVLKVLTTGLPALISWIKRKRQQ-NH。蜂毒素与脂双层膜结合,折叠成两亲性 α-螺旋二级结构,并破坏通透性屏障。自从蜂毒素首次被描述以来,它在生物学和医学领域的一系列惊人的活性和潜在应用已经被描述。蜂毒素也是生物物理学家研究肽和蛋白质在膜中的结构、折叠和功能的首选模型系统。蜂毒素也被用作在膜中进化新活性的模板。在这里,我们概述了对蜂毒素多种活性的丰富的科学研究历史,并概述了令人兴奋的未来应用。

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1
Applications and evolution of melittin, the quintessential membrane active peptide.蜂毒素的应用与演变:一种典型的膜活性肽。
Biochem Pharmacol. 2021 Nov;193:114769. doi: 10.1016/j.bcp.2021.114769. Epub 2021 Sep 17.
2
Melittin: a membrane-active peptide with diverse functions.蜂毒肽:一种具有多种功能的膜活性肽。
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Thermodynamics of melittin binding to lipid bilayers. Aggregation and pore formation.蜂毒素与脂质双层结合的热力学。聚集与孔形成。
Biochemistry. 2009 Mar 31;48(12):2586-96. doi: 10.1021/bi802127h.
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Folding of amphipathic alpha-helices on membranes: energetics of helix formation by melittin.两亲性α螺旋在膜上的折叠:蜂毒肽形成螺旋的能量学
J Mol Biol. 1999 Jan 29;285(4):1363-9. doi: 10.1006/jmbi.1998.2346.
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Functional characterization of naturally occurring melittin peptide isoforms in two honey bee species, Apis mellifera and Apis cerana.两种蜜蜂(西方蜜蜂和中华蜜蜂)中天然存在的蜂毒肽肽异构体的功能表征。
Peptides. 2014 Mar;53:185-93. doi: 10.1016/j.peptides.2014.01.026. Epub 2014 Feb 8.
6
The effect of cyclization of magainin 2 and melittin analogues on structure, function, and model membrane interactions: implication to their mode of action.蛙皮素2和蜂毒素类似物环化对结构、功能及与模型膜相互作用的影响:对其作用模式的启示
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The actions of melittin on membranes.蜂毒肽对细胞膜的作用。
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8
Influence of the lipid composition on the kinetics of concerted insertion and folding of melittin in bilayers.脂质组成对蜂毒素在双层膜中协同插入和折叠动力学的影响。
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Effect of succinylation on the membrane activity and conformation of a short cecropin A-melittin hybrid peptide.琥珀酰化对短天蚕素A-蜂毒素杂合肽的膜活性和构象的影响
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Spectroscopic and computational study of melittin, cecropin A, and the hybrid peptide CM15.蜂毒素、抗菌肽 A 和杂合肽 CM15 的光谱和计算研究。
J Phys Chem B. 2012 Sep 6;116(35):10600-8. doi: 10.1021/jp304021t. Epub 2012 Jul 30.

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本文引用的文献

1
Reversible blood-brain barrier opening utilizing the membrane active peptide melittin in vitro and in vivo.利用膜活性肽蜂毒素在体外和体内实现可逆转的血脑屏障开放。
Biomaterials. 2021 Aug;275:120942. doi: 10.1016/j.biomaterials.2021.120942. Epub 2021 Jun 10.
2
pH-triggered pore-forming peptides with strong composition-dependent membrane selectivity.具有强组成依赖性膜选择性的 pH 触发的孔形成肽。
Biophys J. 2021 Feb 16;120(4):618-630. doi: 10.1016/j.bpj.2021.01.010. Epub 2021 Jan 16.
3
The Mechanism of Membrane Permeabilization by Peptides: Still an Enigma.肽介导的膜通透性机制:仍是一个谜。
Aust J Chem. 2019;73(3):96-103. doi: 10.1071/CH19449. Epub 2019 Nov 11.
4
Synthetic molecular evolution of host cell-compatible, antimicrobial peptides effective against drug-resistant, biofilm-forming bacteria.宿主细胞相容的、抗微生物肽的人工分子进化,有效对抗耐药、形成生物膜的细菌。
Proc Natl Acad Sci U S A. 2020 Apr 14;117(15):8437-8448. doi: 10.1073/pnas.1918427117. Epub 2020 Apr 2.
5
Targeted Delivery of Secretory Promelittin via Novel Poly(lactone--β-amino ester) Nanoparticles for Treatment of Breast Cancer Brain Metastases.通过新型聚(内酯-β-氨基酯)纳米颗粒靶向递送分泌型前催乳素用于治疗乳腺癌脑转移
Adv Sci (Weinh). 2020 Jan 19;7(5):1901866. doi: 10.1002/advs.201901866. eCollection 2020 Mar.
6
Melittin-lipid nanoparticles target to lymph nodes and elicit a systemic anti-tumor immune response.蜂毒素脂质纳米粒靶向淋巴结并引发全身性抗肿瘤免疫反应。
Nat Commun. 2020 Feb 28;11(1):1110. doi: 10.1038/s41467-020-14906-9.
7
Apoptotic Effects of Melittin on 4T1 Breast Cancer Cell Line is associated with Up Regulation of Mfn1 and Drp1 mRNA Expression.蜂毒素对 4T1 乳腺癌细胞系的凋亡作用与 Mfn1 和 Drp1 mRNA 表达上调有关。
Anticancer Agents Med Chem. 2020;20(7):790-799. doi: 10.2174/1871520620666200211091451.
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Melittin-A Natural Peptide from Bee Venom Which Induces Apoptosis in Human Leukaemia Cells.蜂毒肽——一种来自蜜蜂毒液的天然肽,可诱导人白血病细胞凋亡。
Biomolecules. 2020 Feb 6;10(2):247. doi: 10.3390/biom10020247.
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Estrone-Decorated Polyion Complex Micelles for Targeted Melittin Delivery to Hormone-Responsive Breast Cancer Cells.雌酮修饰的聚离子复合物胶束用于靶向递送至激素响应性乳腺癌细胞的蜂毒素
Biomacromolecules. 2020 Mar 9;21(3):1222-1233. doi: 10.1021/acs.biomac.9b01681. Epub 2020 Feb 24.
10
Melittin inhibits proliferation, migration and invasion of bladder cancer cells by regulating key genes based on bioinformatics and experimental assays.蜂毒素通过基于生物信息学和实验检测的关键基因调控抑制膀胱癌细胞的增殖、迁移和侵袭。
J Cell Mol Med. 2020 Jan;24(1):655-670. doi: 10.1111/jcmm.14775. Epub 2019 Nov 5.