Saffarian Delkhosh Arvin, Hadadianpour Elaheh, Islam Md Majharul, Georgieva Elka R
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409, USA.
J Struct Biol X. 2024 Dec 11;11:100117. doi: 10.1016/j.yjsbx.2024.100117. eCollection 2025 Jun.
We investigated several small viral proteins that reside and function in cellular membranes. These proteins belong to the viroporin family because they assemble into ion-conducting oligomers. However, despite forming similar oligomeric structures with analogous functions, these proteins have diverse amino acid sequences. In particular, the amino acid compositions of the proposed channel-forming transmembrane (TM) helices are vastly different-some contain residues (e.g., His, Trp, Asp, Ser) that could facilitate cation transport. Still, other viroporins' TM helices encompass exclusively hydrophobic residues; therefore, it is difficult to explain their channels' activity, unless other mechanisms (e.g., involving a negative lipid headgroups and/or membrane destabilization) take place. For this study, we selected the M2, Vpu, E, p13II, p7, and 2B proteins from the influenza A, HIV-1, human T-cell leukemia, hepatitis C, and picorna viruses, respectively. We provide a brief overview of the current knowledge about these proteins' structures as well as remaining questions about more comprehensive understanding of their structures, conformational dynamics, and function. Finally, we outline strategies to utilize a multi-prong structural and computational approach to overcome current deficiencies in the knowledge about these proteins.
我们研究了几种存在于细胞膜并在其中发挥作用的小病毒蛋白。这些蛋白属于病毒离子通道蛋白家族，因为它们能组装成离子传导寡聚体。然而，尽管这些蛋白形成了具有类似功能的相似寡聚结构，但它们的氨基酸序列却各不相同。特别是，推测的形成通道的跨膜（TM）螺旋的氨基酸组成差异很大——有些含有可能促进阳离子运输的残基（如组氨酸、色氨酸、天冬氨酸、丝氨酸）。不过，其他病毒离子通道蛋白的TM螺旋仅包含疏水残基；因此，很难解释它们通道的活性，除非发生其他机制（如涉及带负电荷的脂质头部基团和/或膜不稳定）。在本研究中，我们分别从甲型流感病毒、HIV-1、人类T细胞白血病病毒、丙型肝炎病毒和小RNA病毒中选择了M2、Vpu、E、p13II、p7和2B蛋白。我们简要概述了目前关于这些蛋白结构的知识，以及在更全面理解它们的结构、构象动力学和功能方面仍然存在的问题。最后，我们概述了利用多管齐下的结构和计算方法来克服目前对这些蛋白认识不足的策略。
