The tetraspanin family plays key roles in many physiological processes, such as, tumour invasion, cell motility, virus infection, cell attachment and entry. Tetraspanins function as molecular scaffolds organized in microdomains with interesting downstream cellular consequences. However, despite their relevance in human physiology, the precise mechanisms of their various functions remain elusive. In particular, the full-length CD81 tetraspanin has interesting cholesterol-related properties that modulate its activity in cells. In this work, we study the opening transition of CD81 under different conditions. We propose that such conformational change is a collaborative process enhanced by simultaneous interactions between multiple identical CD81 tetraspanins. With molecular dynamics simulations we describe the crucial role of a ternary lipid bilayer with cholesterol in CD81 conformational dynamics, observing two emergent properties: first, clusters of CD81 collectively segregate one tetraspanin while favouring one opening transition, second, cumulative cholesterol sequestering by CD81 tetraspanins inhibits large membrane deformations due to local density variations.

四跨膜蛋白家族在许多生理过程中起关键作用，例如肿瘤侵袭、细胞运动、病毒感染、细胞附着和进入。Tetraspanins 作为分子支架组织在微域中，具有有趣的下游细胞后果。然而，尽管它们与人类生理学相关，但它们各种功能的确切机制仍然难以捉摸。特别是，全长 CD81 四跨膜蛋白具有有趣的胆固醇相关特性，可调节其在细胞中的活性。在这项工作中，我们研究了 CD81 在不同条件下的开放转变。我们提出，这种构象变化是一个协作过程，通过多个相同的 CD81 四跨膜蛋白之间的同时相互作用增强。