Structural Studies Of Hiv Proteins

根据世界卫生组织的数据，2002年，全世界有500万人新感染了人体免疫缺陷病毒（艾滋病毒），导致总共有4 200万人感染艾滋病毒或患有后天免疫缺陷综合症（艾滋病）。像许多其他感染一样，HIV通过大量产生抗原识别抗体（Abs）引发免疫系统的反应。然而，最终免疫系统无法控制病毒，导致艾滋病的发病。在某些情况下，患者会产生中和抗体，因此不会发展为艾滋病。这些中和抗体已显示主要靶向病毒表面蛋白。抗原性蛋白表达为env-蛋白gp 160，其随后裂解为包膜糖蛋白gp 120和跨膜蛋白gp 41。成熟蛋白的某些区域在感染的某些阶段或在病毒碎片中通过构象变化而暴露，并诱导中和抗体的形成。中和抗体识别的区域在开发抑制HIV感染的药物或疫苗方面具有特殊意义。此外，有关积极参与感染过程的蛋白质复合物中相互作用表面的信息也可以导致疫苗候选人以及更好地了解该过程本身。 蛋白质复合物（如抗体：抗原）中相互作用表面的生物物理特性应有助于了解蛋白质如何识别其结合伴侣，并有助于了解这些分子如何实现其体内功能。因此，MS工作组的中心研究计划是开发和应用基于质谱的技术来确定蛋白质复合物中的相互作用表面。 我们正在表征的特定相互作用包括：HIV rgp 120/gp 40与hrCD 4（趋化因子受体）和人抗HIV单克隆抗体的相互作用;以及HIV rp 24与MAb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.