Homsi Yahya, Schloetel Jan-Gero, Scheffer Konstanze D, Schmidt Thomas H, Destainville Nicolas, Florin Luise, Lang Thorsten
Department of Membrane Biochemistry, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Department of Medical Microbiology and Hygiene, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.
Biophys J. 2014 Jul 1;107(1):100-13. doi: 10.1016/j.bpj.2014.05.028.
CD81 is a ubiquitously expressed member of the tetraspanin family. It forms large molecular platforms, so-called tetraspanin webs that play physiological roles in a variety of cellular functions and are involved in viral and parasite infections. We have investigated which part of the CD81 molecule is required for the formation of domains in the cell membranes of T-cells and hepatocytes. Surprisingly, we find that large CD81 platforms assemble via the short extracellular δ-domain, independent from a strong primary partner binding and from weak interactions mediated by palmitoylation. The δ-domain is also essential for the platforms to function during viral entry. We propose that, instead of stable binary interactions, CD81 interactions via the small δ-domain, possibly involving a dimerization step, play the key role in organizing CD81 into large tetraspanin webs and controlling its function.
CD81是四跨膜蛋白家族中广泛表达的成员。它形成大分子平台，即所谓的四跨膜蛋白网络，在多种细胞功能中发挥生理作用，并参与病毒和寄生虫感染。我们研究了CD81分子的哪一部分是T细胞和肝细胞细胞膜中结构域形成所必需的。令人惊讶的是，我们发现大型CD81平台通过短的细胞外δ结构域组装，独立于强的主要伴侣结合以及棕榈酰化介导的弱相互作用。δ结构域对于平台在病毒进入过程中发挥功能也是必不可少的。我们提出，通过小的δ结构域的CD81相互作用，可能涉及二聚化步骤，而不是稳定的二元相互作用，在将CD81组织成大型四跨膜蛋白网络并控制其功能方面起关键作用。
