Nijenhuis M, Hämmerling G J
Department of Molecular Immunology, German Cancer Research Center, Heidelberg, Germany.
J Immunol. 1996 Dec 15;157(12):5467-77.
The transporter associated with Ag processing (TAP) translocates cytosolic peptides into the endoplasmic reticulum, where they can bind to MHC class I molecules. TAP does not translocate all peptides with equal efficiency, but selects peptides with regard to both their length and their sequence and, in this manner, affects the pool of peptides available for binding to MHC class I molecules. It has been demonstrated that peptide selection by TAP predominantly occurs during the first step in the translocation process, namely the association of the peptide with a binding site present on the TAP molecule. In this study, we identify four regions, two on the TAP1 and two on the TAP2 subunit, that make major contributions to this binding site. For both TAP1 and TAP2, the identified regions overlap with the cytosol-membrane boundaries of the two transmembrane segments closest to the ATP binding site. Our data are consistent with a model in which the transmembrane segments of TAP form a pore in the membrane, with the peptide binding site being formed by the cytosolic mouth of this pore.
与抗原加工相关的转运体（TAP）将胞质肽转运至内质网，在那里它们可以与MHC I类分子结合。TAP并非以同等效率转运所有肽段，而是根据肽段的长度和序列进行选择，从而影响可用于与MHC I类分子结合的肽段库。已经证明，TAP对肽段的选择主要发生在转运过程的第一步，即肽段与TAP分子上存在的结合位点结合时。在本研究中，我们确定了四个区域，TAP1上有两个，TAP2亚基上有两个，它们对该结合位点有主要贡献。对于TAP1和TAP2，所确定的区域与最靠近ATP结合位点的两个跨膜片段的胞质-膜边界重叠。我们的数据与一个模型一致，即TAP的跨膜片段在膜中形成一个孔，肽段结合位点由该孔的胞质口形成。
