Type I and type V procollagen triple helix uses different subsets of the molecular ensemble for lysine posttranslational modifications in the rER.
Type I and type V procollagen triple helix uses different subsets of the molecular ensemble for lysine posttranslational modifications in the rER.
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DOI：
10.1016/j.jbc.2021.100453
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Bächinger HP
中科院分区：
文献类型：
--
作者：
Ishikawa Y;Taga Y;Zientek K;Mizuno N;Salo AM;Semenova O;Tufa SF;Keene DR;Holden P;Mizuno K;Gould DB;Myllyharju J;Bächinger HP
胶原蛋白是人体最丰富的蛋白质。它具有特征性的三螺旋结构，并且经过大量翻译后修饰。胶原蛋白的复杂生物合成涉及粗面内质网中许多酶和分子伴侣的加工。赖氨酰羟化酶 1 (LH1) 需要羟化赖氨酸，以实现胶原蛋白三螺旋序列内的交联和碳水化合物附着。此外，最近对脯氨酰 3-羟化酶 3 (P3H3) 的研究表明，该酶可能对 LH1 活性至关重要。然而，有关其参与的细节仍不清楚。如果 P3H3 是对 LH1 活性至关重要的 LH1 伴侣，则 P3H3 和 LH1 缺失小鼠应表现出类似的赖氨酰羟基化缺陷。为了检验这一假设，我们比较了 P3H3 null、LH1 null 和野生型小鼠的 V 型和 I 型胶原三螺旋结构域中羟基赖氨酸的含量和位置。在 P3H3 缺失小鼠中，V 型胶原蛋白中的羟赖氨酸含量减少，但令人惊讶的是，来自 LH1 缺失小鼠的 V 型胶原蛋白含有与来自野生型小鼠的 V 型胶原蛋白一样多的羟赖氨酸。在 I 型胶原蛋白中，我们的结果表明 LH1 在赖氨酰羟基化中发挥全局酶促作用。 P3H3 也参与赖氨酰羟基化，特别是在交联形成位点，但并非所有赖氨酰羟基化位点都需要。总之，我们的研究表明，LH1 和 P3H3 可能具有两种不同的机制来识别不同的胶原类型并将交联形成位点与 I 型胶原中的其他位点区分开来。
Collagen is the most abundant protein in humans. It has a characteristic triple-helix structure and is heavily posttranslationally modified. The complex biosynthesis of collagen involves processing by many enzymes and chaperones in the rough endoplasmic reticulum. Lysyl hydroxylase 1 (LH1) is required to hydroxylate lysine for cross-linking and carbohydrate attachment within collagen triple helical sequences. Additionally, a recent study of prolyl 3-hydroxylase 3 (P3H3) demonstrated that this enzyme may be critical for LH1 activity; however, the details surrounding its involvement remain unclear. If P3H3 is an LH1 chaperone that is critical for LH1 activity, P3H3 and LH1 null mice should display a similar deficiency in lysyl hydroxylation. To test this hypothesis, we compared the amount and location of hydroxylysine in the triple helical domains of type V and I collagen from P3H3 null, LH1 null, and wild-type mice. The amount of hydroxylysine in type V collagen was reduced in P3H3 null mice, but surprisingly type V collagen from LH1 null mice contained as much hydroxylysine as type V collagen from wild-type mice. In type I collagen, our results indicate that LH1 plays a global enzymatic role in lysyl hydroxylation. P3H3 is also involved in lysyl hydroxylation, particularly at cross-link formation sites, but is not required for all lysyl hydroxylation sites. In summary, our study suggests that LH1 and P3H3 likely have two distinct mechanisms to recognize different collagen types and to distinguish cross-link formation sites from other sites in type I collagen.
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影响因子：
4.5
作者：
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