Lysyl hydroxylase 2 mediated collagen post-translational modifications and functional outcomes.
Lysyl hydroxylase 2 mediated collagen post-translational modifications and functional outcomes.
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DOI：
10.1038/s41598-022-18165-0
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发表时间：
2022-08-22
影响因子：
4.6
通讯作者：
Yamauchi, Mitsuo
中科院分区：
文献类型：
--
作者：
Terajima, Masahiko;Taga, Yuki;Nakamura, Tomoyuki;Guo, Hou-Fu;Kayashima, Yukako;Maeda-Smithies, Nobuyo;Parag-Sharma, Kshitij;Kim, Jeong Seon;Amelio, Antonio L.;Mizuno, Kazunori;Kurie, Jonathan M.;Yamauchi, Mitsuo
赖氨酰羟化酶2（Lysyl hydroxylase 2，LH 2）是LH家族的一员，催化胶原蛋白上赖氨酸（lysine，Lys）的羟化，与多种疾病有关。虽然其作为端肽基LH的功能被普遍接受，但几个基本问题仍然没有答案：1。LH 2是否催化胶原蛋白所有端肽基赖氨酸残基的羟基化？2. LH 2是否参与螺旋赖氨酸羟基化？3.当LH 2完全缺失时，功能后果是什么？为了回答这些问题，我们产生了LH 2-null MC 3 T3细胞（LH 2KO），并与对照组相比，广泛表征了I型胶原表型。交联分析表明，羟基赖氨酸-醛（Hylald）衍生的交联完全不存在于LH 2 KO胶原蛋白中，同时增加了Lysald衍生的交联。质谱分析表明，在LH 2KO I型胶原蛋白，端肽基赖氨酸羟基化被完全废除在所有网站，而螺旋赖氨酸羟基化略有减少，在一个特定的网站的方式。此外，二糖基化的Hyl以单糖基化的Hyl为代价而减少。LH 2KO胶原蛋白是高度可溶性和可消化的，原纤维直径减少，矿化受损时，与对照组相比。总之，这些数据强调了LH 2催化的胶原蛋白修饰在MC 3 T3细胞中胶原蛋白稳定性、组织和矿化中的关键作用。
Lysyl hydroxylase 2 (LH2) is a member of LH family that catalyzes the hydroxylation of lysine (Lys) residues on collagen, and this particular isozyme has been implicated in various diseases. While its function as a telopeptidyl LH is generally accepted, several fundamental questions remain unanswered: 1. Does LH2 catalyze the hydroxylation of all telopeptidyl Lys residues of collagen? 2. Is LH2 involved in the helical Lys hydroxylation? 3. What are the functional consequences when LH2 is completely absent? To answer these questions, we generated LH2-null MC3T3 cells (LH2KO), and extensively characterized the type I collagen phenotypes in comparison with controls. Cross-link analysis demonstrated that the hydroxylysine-aldehyde (Hylald)-derived cross-links were completely absent from LH2KO collagen with concomitant increases in the Lysald-derived cross-links. Mass spectrometric analysis revealed that, in LH2KO type I collagen, telopeptidyl Lys hydroxylation was completely abolished at all sites while helical Lys hydroxylation was slightly diminished in a site-specific manner. Moreover, di-glycosylated Hyl was diminished at the expense of mono-glycosylated Hyl. LH2KO collagen was highly soluble and digestible, fibril diameters were diminished, and mineralization impaired when compared to controls. Together, these data underscore the critical role of LH2-catalyzed collagen modifications in collagen stability, organization and mineralization in MC3T3 cells.
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DOI：
10.1016/j.jbc.2021.100453
发表时间：
2021-01
期刊：
The Journal of biological chemistry
影响因子：
--
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
通讯作者：
Bächinger HP
影响因子：
4.5
作者：
Heard ME;Besio R;Weis M;Rai J;Hudson DM;Dimori M;Zimmerman SM;Kamykowski JA;Hogue WR;Swain FL;Burdine MS;Mackintosh SG;Tackett AJ;Suva LJ;Eyre DR;Morello R
通讯作者：
Morello R
影响因子：
4.5
作者：
Cabral WA;Perdivara I;Weis M;Terajima M;Blissett AR;Chang W;Perosky JE;Makareeva EN;Mertz EL;Leikin S;Tomer KB;Kozloff KM;Eyre DR;Yamauchi M;Marini JC
通讯作者：
Marini JC
DOI：
10.1073/pnas.1600074113
发表时间：
2016-06-28
影响因子：
11.1
作者：
Gjaltema, Rutger A. F.;van der Stoel, Miesje M.;Bank, Ruud A.
通讯作者：
Bank, Ruud A.
影响因子：
30.8
作者：
Cabral, Wayne A.;Chang, Weizhong;Marini, Joan C.
通讯作者：
Marini, Joan C.