Extracellular crosslinking mass spectrometry reveals HLA class I - HLA class II interactions on the cell surface
Extracellular crosslinking mass spectrometry reveals HLA class I - HLA class II interactions on the cell surface
复制标题
DOI：
10.1016/j.molimm.2021.05.010
复制
发表时间：
2021-05-27
影响因子：
3.6
通讯作者：
Wu, Wei
中科院分区：
文献类型：
--
作者：
Armony, Gad;Heck, Albert J. R.;Wu, Wei
人类白细胞抗原（HLA）复合物是重要的细胞表面蛋白组装体，有助于T细胞监视体内几乎所有类型的细胞。虽然T细胞受体与HLA I类和II类复合物的结合被详细的结构信息很好地描述，但所调查细胞的质膜内的顺式HLA相互作用的性质仍有待更好地表征，因为膜环境中的蛋白质-蛋白质相互作用在技术上具有挑战性。在这里，我们进行了细胞外化学交联完整的抗原呈递细胞，以具体阐明蛋白质-蛋白质相互作用存在于外部质膜。我们发现交联数据集主要由涉及HLA分子的蛋白质间和蛋白质内交联组成，这不仅能够构建以HLA为中心的质膜蛋白相互作用图谱，而且还揭示了HLA I类- HLA II类相互作用的多种模式，并基于交联剂距离限制进行了进一步的结构建模。总的来说，我们的数据表明，HLA分子共定位，可以密集地包装在质膜上。
Human Leukocyte Antigen (HLA) complexes are critical cell-surface protein assemblies that facilitate T-cell surveillance of almost all cell types in the body. While T-cell receptor binding to HLA class I and class II complexes is well-described with detailed structural information, the nature of cis HLA interactions within the plasma membrane of the surveyed cells remains to be better characterized, as protein-protein interactions in the membrane environment are technically challenging to profile. Here we performed extracellular chemical crosslinking on intact antigen presenting cells to specifically elucidate protein-protein interactions present in the external plasma membrane. We found that the crosslink dataset was dominated by inter- and intra-protein crosslinks involving HLA molecules, which enabled not only the construction of an HLA-centric plasma membrane protein interaction map, but also revealed multiple modes of HLA class I - HLA class II interactions with further structural modeling based on crosslinker distance restraints. Collectively, our data demonstrate that HLA molecules colocalize and can be densely packed on the plasma membrane.