Structural Studies Of Hiv Proteins

根据世界卫生组织的数据，2002年，全世界有500万人新感染了人类免疫缺陷病毒(艾滋病毒)，导致总共有4200万人感染了艾滋病毒或获得性自身免疫缺陷综合症(艾滋病)。像许多其他感染一样，艾滋病毒通过大量产生抗原识别抗体(Abs)来触发免疫系统的反应。然而，最终免疫系统无法控制病毒，导致艾滋病的发作。在某些情况下，患者会产生中和性抗体，因此不会患上艾滋病。这些中和抗体已被证明主要针对病毒表面蛋白。抗原蛋白被表达为包膜蛋白gp160，随后被切割成包膜糖蛋白gp120和跨膜蛋白gp41。在感染的某些阶段或在病毒碎片中，成熟蛋白的某些区域因构象变化而暴露，并诱导中和抗体的形成。中和抗体识别的区域在开发抑制艾滋病毒感染的药物或疫苗方面特别有意义。此外，有关积极参与感染过程的蛋白质复合体中相互作用表面的信息也可以帮助候选疫苗以及更好地了解这一过程本身。 蛋白质复合体中相互作用表面的生物物理特征，如抗体：抗原，应有助于深入了解蛋白质如何识别其结合伙伴，并有助于理解这些分子如何在体内发挥其功能。因此，MS工作组的中心研究计划一直是开发和应用基于质谱学的技术来确定蛋白质复合体中的相互作用表面。 我们描述的具体相互作用包括：HIV rgp120/gp40与趋化因子受体hrCD4的相互作用，以及与人类抗HIV单抗的相互作用；以及HIV rp24与单抗的相互作用。

According to the World Health Organization, in the year 2002, 5 million people worldwide were newly infected with the human immunodeficiency virus (HIV) resulting in a total of 42 million people living with HIV or the acquired autoimmune deficiency syndrome (AIDS). Like many other infections, HIV triggers a response by the immune system via the massive production of antigen-recognizing antibodies (Abs). However, ultimately the immune system fails to control the virus, leading to the onset of AIDS. In some cases, patients develop neutralizing Abs and, consequently, do not develop AIDS. These neutralizing Abs have been shown to primarily target viral surface proteins. The antigenic proteins are expressed as the env-protein gp160 which is subsequently cleaved into the envelope glycoprotein gp120 and the transmembrane protein gp41. Some regions of the mature proteins are exposed by conformational changes during certain stages of infection or in viral debris, and induce formation of neutralizing Abs. The regions recognized by neutralizing Abs are of special interest in respect to developing drugs or vaccines that inhibit infection by HIV. Additionally, information about the interacting surfaces in the protein complexes actively involved in the infection process can also lead to vaccine candidates as well as a better understanding of the process itself. The biophysical characterization of the surfaces of interaction in protein complexes, such as antibody:antigen, should provide insight into how proteins recognize their binding partners and should aid in understanding how these molecules fulfill their in vivo functions. Therefore, the central research program of the MS Workgroup has been to develop and apply mass spectrometry-based techniques to determining the interaction surfaces in protein complexes. The specific interactions we are characterizing include: interactions of HIV rgp120/gp40 with the hrCD4, the chemokine receptor, and with human anti-HIV monoclonal antibodies; and HIV rp24 interactions with MAbs.