Trimming of TAP-translocated peptides in the endoplasmic reticulum and in the cytosol during recycling.
Trimming of TAP-translocated peptides in the endoplasmic reticulum and in the cytosol during recycling.
复制标题
DOI：
10.1084/jem.180.5.1591
复制
发表时间：
1994-11-01
期刊：
影响因子：
--
通讯作者：
Neefjes J
中科院分区：
文献类型：
--
作者：
Roelse J;Grommé M;Momburg F;Hämmerling G;Neefjes J
细胞质肽通过与抗原加工相关的转运蛋白（TAP）转运到内质网（ER）管腔，其中主要的组织相容性复合体（MHC） I类分子与约8-10个氨基酸的肽相关。TAP易位的9-13个氨基酸的肽具有最高的相对亲和力，但也有较长和较短的肽。由于不正确的序列或长度而不能与I类分子结合的肽的命运是未知的。在这里，我们发现大部分易位肽通过一种需要三磷酸腺苷（ATP）的机制迅速从内质网释放出来，而GTP γ s不能抑制这一机制。尽管游离肽在内质网腔中被缓慢修剪，但它们在细胞质中被迅速降解。从内质网释放的一小部分肽逃脱了在细胞质溶胶中的完全降解，并以tap依赖的方式再循环回到内质网。这些结果表明，太长而不能与内质网I类分子结合的肽可以在内质网腔中进一步修剪，或者可以被运输回细胞质，其中一部分肽被修剪到适合与MHC I类分子结合的大小，并再循环回内质网。
Cytosolic peptides are translocated to the endoplasmic reticulum (ER) lumen by the transporters associated with antigen processing (TAP), where major histocompatibility complex (MHC) class I molecules associate with peptides of about 8-10 amino acids. TAP translocates peptides of 9-13 amino acids with the highest relative affinity but also longer and shorter peptides. The fate of the peptides that fail to associate with class I molecules because of incorrect sequence or length, is unknown. Here we show that the bulk of the translocated peptides are rapidly released from the ER by a mechanism that requires adenosine triphosphate (ATP) and that could not be inhibited by GTP gamma S. TAP does not appear to be involved in this process. Whereas free peptides are slowly trimmed in the ER lumen, they are rapidly degraded in the cytosol. A fraction of the peptides released from the ER escapes complete degradation in the cytosol and recycles back to the ER in a TAP-dependent fashion. These results suggest that peptides that are too long for binding to class I molecules in the ER can be trimmed further in the ER lumen or, alternatively, can be transported back to the cytosol where a fraction of the peptides is trimmed to a size suitable for association to MHC class I molecules and recycles back to the ER.