Bovine spleen multicatalytic proteinase complex (proteasome) - Replacement of X, Y, and Z subunits by LMP7, LMP2, and MECL1 and changes in properties and specificity
Bovine spleen multicatalytic proteinase complex (proteasome) - Replacement of X, Y, and Z subunits by LMP7, LMP2, and MECL1 and changes in properties and specificity
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DOI：
10.1074/jbc.272.18.11824
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发表时间：
1997-05-02
影响因子：
4.8
通讯作者：
Orlowski, M
中科院分区：
文献类型：
--
作者：
Eleuteri, AM;Kohanski, RA;Orlowski, M
从牛脾脏分离的多催化蛋白酶复合物（MPC）亚基的氨基酸测序显示，干扰素γ诱导的LMP7、LMP2和MECL1亚基几乎完全取代了在大多数组织中组成性表达的X、Y和Z亚基。与垂体MPC比较发现胰凝乳酶样活性降低，肽酰谷氨酰肽水解活性降低，并且具有与垂体支链氨基酸偏好（BrAAP）成分相似但不相同的特性的高活性成分。与垂体BrAAP成分不同，脾脏MPC对P-1位支链或芳香氨基酸残基的底物的k -m显著降低，催化效率（k(cat)）显著提高，特异性常数（k(cat)/ k -m）提高80-180倍。此外，与垂体的BrAAP成分不同，脾脏的BrAAP对3,4-二氯异香豆素的失活敏感，对具有苯丙氨酸或白氨酸残基的肽基醛的抑制敏感。几个苯丙氨酸肽醛被鉴定有选择性地抑制脾脏成分，但不抑制垂体MPC。其中两种抑制剂是二肽基醛，另外两种是四肽基醛，其Pro残基位于P-3位置。讨论了脾脏MPC的特性和特异性是干扰素- γ诱导亚单位存在的结果的可能性。
Amino acid sequencing of subunits of the multicatalytic proteinase complex (MPC) isolated from bovine spleen showed an almost complete replacement of the X, Y, and Z subunits, constitutively expressed in most tissues, by the interferon-gamma-inducible LMP7, LMP2, and MECL1 subunits. A comparison with the pituitary MPC found a decreased chymotrypsin-like activity, a depressed peptidylglutamyl-peptide hydrolyzing activity, and a highly active component with properties similar to, but not identical with, that of the pituitary branched chain amino acid preferring (BrAAP) component. Unlike the pituitary BrAAP component, that of the spleen MPC exhibited a greatly decreased K-m, a highly increased catalytic efficiency (k(cat)), and a 80-180 times greater specificity constant (k(cat)/K-m) toward substrates with either branched chain or aromatic amino acid residues in the P-1 position. Also, unlike the pituitary BrAAP component, that of the spleen was sensitive to inactivation by 3,4-dichloroisocoumarin and sensitive to inhibition by peptidyl-aldehydes with either phenylalaninal or leucinal residues. Several phenylalaninal peptidyl-aldehydes were identified which selectively inhibited components of the spleen but not of the pituitary MPC. Two of the inhibitors are dipeptidyl-aldehydes, two others are tetrapeptidyl-aldehydes with a Pro residue in the P-3 position. The possibility is discussed that the properties and specificity of the spleen MPC are a consequence of the presence of the interferon-gamma-inducible subunits.