Dimerization of human lysyl hydroxylase 3 (LH3) is mediated by the amino acids 541-547
Dimerization of human lysyl hydroxylase 3 (LH3) is mediated by the amino acids 541-547
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DOI：
10.1016/j.matbio.2010.10.002
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发表时间：
2011-01-01
期刊：
影响因子：
6.9
通讯作者：
Myllyla, Raili
中科院分区：
文献类型：
--
作者：
Heikkinen, Jari;Risteli, Maija;Myllyla, Raili
赖氨酰羟化酶（LH）催化胶原和胶原样蛋白中赖氨酸的翻译后修饰，其功能为二聚体。然而，负责二聚化的氨基酸和二聚体形成在LH的酶活性中的作用尚未确定。我们已经本地化的赖氨酰羟化酶3（LH 3），胶原蛋白生物合成的多功能酶，二聚化的区域负责之间的糖基转移酶活性和赖氨酰羟化酶活性结构域的氨基酸序列。该区域由人LH 3中的氨基酸541-547覆盖，但不含半胱氨酸残基。该区域在LH亚型中高度保守，并且还参与LH 1亚基的二聚化。二聚化是LH 3的LH活性所必需的，而它不是糖基转移酶活性所必需的。为了确定复合物的形成是否可以发生在来自不同物种的LH分子之间，以及不同的LH亚型之间，在杆状病毒系统中产生双表达。通过蛋白质印迹分析检测小鼠和人LH 3之间、人LH 1和LH 3之间以及人LH 2和LH 3之间的异源复合物形成。然而，由于形成的复合物的量低，杂合物的体内功能仍然不清楚。(c)2010 Elsevier B. V.保留所有权利。
Lysyl hydroxylases (LH), which catalyze the post-translational modifications of lysines in collagen and collagen-like proteins, function as dimers. However, the amino acids responsible for dimerization and the role of dimer formation in the enzymatic activities of LH have not yet been identified. We have localized the region responsible for the dimerization of lysyl hydroxylase 3 (LH3), a multifunctional enzyme of collagen biosynthesis, to a sequence of amino acids between the glycosyltransferase activity and the lysyl hydroxylase activity domains. This area is covered by amino acids 541-547 in human LH3, but contains no cysteine residues. The region is highly conserved among LH isoforms, and is also involved in the dimerization of LH1 subunits. Dimerization is required for the LH activity of LH3, whereas it is not obligatory for the glycosyltransferase activities. In order to determine whether complex formation can occur between LH molecules originating from different species, and between different LH isoforms, double expressions were generated in a baculovirus system. Heterocomplex formation between mouse and human LH3, between human LH1 and LH3 and between human LH2 and LH3 was detected by western blot analyses. However, due to the low amount of complexes formed, the in vivo function of heterocomplexes remains unclear. (c) 2010 Elsevier B.V. All rights reserved.