2 PUTATIVE SUBUNITS OF A PEPTIDE PUMP ENCODED IN THE HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II REGION
2 PUTATIVE SUBUNITS OF A PEPTIDE PUMP ENCODED IN THE HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II REGION
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DOI：
10.1073/pnas.88.22.10094
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发表时间：
1991-11-01
影响因子：
11.1
通讯作者：
SPIES, T
中科院分区：
文献类型：
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作者：
BAHRAM, S;ARNOLD, D;SPIES, T
人类主要组织相容性复合物 (MHC) 的 II 类区域可能编码一些控制内源抗原加工和 MHC I 类分子向细胞毒性 T 淋巴细胞呈递肽表位的基因。先前描述的肽供应因子 (PSF1) 是转运蛋白多药耐药家族的成员，可以将胞质肽泵入 I 类分子组装的膜结合区室中。第二个转运蛋白基因 PSF2 距离 PSF1 10 KB，靠近 II 类 DOB 基因。 PSF1 和 PSF2 的完整序列由 cDNA 克隆确定。翻译产物在序列和预测的二级结构上密切相关。两者都含有高度保守的 ATP 结合折叠，并且在疏水结构域中具有 25% 的同源性，其中跨膜片段的数量暂定为 8 个。基于其他转运蛋白中这两个结构域的二聚体组织原理，PSF1 和 PSF2 可以作为互补亚基发挥作用，也可以独立地作为同二聚体发挥作用，或者两者兼而有之。结合之前的遗传证据，γ-干扰素对 PSF1 和 PSF2 的共同调节以及这些基因在某种程度上的协调转录表明，尽管不能排除 PSF2 的独特功能，但它们在 I 类分子的肽装载中具有共同作用。
The class II region of the human major histocompatibility complex (MHC) may encode several genes controlling the processing of endogenous antigen and the presentation of peptide epitopes by MHC class I molecules to cytotoxic T lymphocytes. A previously described peptide supply factor (PSF1) is a member of the multidrug-resistance family of transporters and may pump cytosolic peptides into the membrane-bound compartment where class I molecules assemble. A second transporter gene, PSF2, was identified 10 kilobases (kb) from PSF1, near the class II DOB gene. The complete sequences of PSF1 and PSF2 were determined from cDNA clones. The translation products are closely related in sequence and predicted secondary structure. Both contain a highly conserved ATP-binding fold and share 25% homology in a hydrophobic domain with a tentative number of eight membrane-spanning segments. Based on the principle dimeric organization of these two domains in other transporters, PSF1 and PSF2 may function as complementary subunits, independently as homodimers, or both. Taken together with previous genetic evidence, the coregulation of PSF1 and PSF2 by gamma-interferon and the to-some-degree coordinate transcription of these genes suggest a common role in peptide-loading of class I molecules, although a distinct function of PSF2 cannot be ruled out.