MHC-LINKED LMP GENE-PRODUCTS SPECIFICALLY ALTER PEPTIDASE ACTIVITIES OF THE PROTEASOME
MHC-LINKED LMP GENE-PRODUCTS SPECIFICALLY ALTER PEPTIDASE ACTIVITIES OF THE PROTEASOME
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DOI：
10.1038/365262a0
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发表时间：
1993-09-16
期刊：
影响因子：
64.8
通讯作者：
MONACO, JJ
中科院分区：
文献类型：
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作者：
DRISCOLL, J;BROWN, MG;MONACO, JJ
蛋白酶体是高度保守的大分子结构，其功能为内肽酶1 -3。它们存在于真核组织的细胞质和细胞核中，由至少14个不同的亚基组成，分子量约为20至32 K。蛋白酶体在选择性降解泛素化和某些非泛素化蛋白质中是必不可少的，作为能量依赖性26 S（1，500 K）蛋白水解复合物的蛋白水解核心。两个蛋白酶体亚基LMP 2和LMP 7（参考文献4-7）在主要组织相容性复合体（MHC）内编码，暗示蛋白酶体参与抗原加工8 -9。在这里，我们确定这两个MHC连接的亚基的功能，通过比较纯化的蛋白酶体含有（LMP+）或缺乏（LMP-）这些组件的蛋白水解活性。我们发现，这两种类型的蛋白酶体具有内肽酶活性对基板承载疏水性，碱性或酸性残基前切割位点（P1位置）和在网站以下的天冬酰胺，甘氨酸和脯氨酸残基。LMP+蛋白酶体对P1处具有疏水性、碱性或天冬酰胺残基的底物的活性远高于LMP-蛋白酶体，而当P1处存在酸性和甘氨酸残基时，它们的活性相当。因此，MHC连接的LMP 2和LMP 7亚基起到放大蛋白酶体的特异性内肽酶活性的作用。
PROTEASOMES are highly conserved macromolecular structures which function as endopeptidases1-3. They are found in the cytoplasm and nucleus of eukaryotic tissues and consist of at least 14 non-identical subunits with molecular masses ranging from approximately 20 to 32K. Proteasomes are essential in the selective degradation of ubiquitinated and certain non-ubiquitinated proteins, acting as the proteolytic core of an energy-dependent 26S (1,500K) proteolytic complex. Two proteasome subunits, LMP2 and LMP7 (refs 4-7), are encoded within the major histocompatibility complex (MHC), implicating proteasomes in antigen processing8-9. Here we determine the function of these two MHC-linked subunits by comparing the proteolytic activities of purified proteasomes containing (LMP+) or lacking (LMP-) these components. We find that proteasomes of both types have endopeptidase activity against substrates bearing hydrophobic, basic or acidic residues immediately preceding the cleavage site (the P1 position) and at sites following asparagine, glycine and proline residues. The activity of LMP+ proteasomes is much higher than that of LMP- proteasomes against substrates with hydrophobic, basic or asparagine residues at P1, whereas their activities are comparable when acidic and glycine residues are present at P1. The MHC-linked LMP2 and LMP7 subunits therefore function to amplify specific endopeptidase activities of the proteasome.