题目：EPR Applications in Biology: Examples from HIV Membrane Protein gp41 and an Antimicrobial AApeptide

报告人：宋利凯 研究员

               美国国家强磁场实验室

时间：2018年5月21日上午10:00

地点：国家脉冲强磁场科学中心C204

报告摘要：

EPR is a powerful tool for biological research. The focus of this work is to develop EPR methods for characterizing biological samples, with specific aims to investigate HIV surface protein gp41 and an antibacterial peptide (AA1). 1). HIV gp41-antibody interaction at the viral membrane interface. The membrane proximal ectodomain region (MPER) of gp41 plays a critical role during the viral fusion process and is a major target of anti-gp41 antibodies and vaccine design. In this study, EPR and NMR techniques were used to define MPER structure on the membrane, MPER-lipid interaction, and how anti-HIV antibodies recognize their membrane-immersed epitopes. The analyses revealed a structurally conserved pair of helices immersed in the viral membrane separated by a flexible hinge. Neutralizing anti-gp41 antibodies disrupt the MPER hinge function by perturbing MPER hinge orientation, and/or extracting part of the MPER from the membrane. These findings have revealed important features of gp41-antibody interaction at the viral membrane interface. 2). Selective membrane disruption mechanism of an antibacterial AApeptide. AApeptides are a new class of antibacterial peptidomimetics that are not prone to antibiotic resistance and are highly resistant to protease degradation. We have characterized the membrane interaction of a lipo-cyclic-gamma-AApeptide (AA1). The analyses revealed that AA1 binding increases the membrane permeability of POPC/POPG liposomes, which mimic negatively charged bacterial membranes. AA1 binding also induces significant lipid lateral-ordering and membrane thinning. In contrast, minimal membrane property changes were observed upon AA1 binding for liposomes mimicking mammalian cell membranes, which consist of neutral lipids and cholesterol. Our findings suggest that AA1 interacts and disrupts bacterial membranes through a “carpet-like” mechanism.

报告人简介：

宋利凯，美国国家高磁场实验室研究员, 2005年获佛罗里达州立大学博士学位，2005至2006年在高磁场实验室作博士后研究，2007至2010年任哈佛大学附属丹娜法伯癌症研究院疫苗所结构生物学中心主任，2010起就任于高磁场实验室。主要从事电子顺磁共振在生物医学领域里的研究。在感染性疾病中膜蛋白及细胞膜与蛋白相互作用机制的研究中取得了重要研究成果，其中包括爱滋病毒膜表面蛋白及其抗体的研究。发表学术论文35篇，其中影响因子>9文章9篇（包括PNAS，Nature子刊，Cell子刊，JACS等权威杂志），被引用超过1200次。

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