Mutants of collagen-specific molecular chaperone Hsp47 causing osteogenesis imperfecta are structurally unstable with weak binding affinity to collagen
Mutants of collagen-specific molecular chaperone Hsp47 causing osteogenesis imperfecta are structurally unstable with weak binding affinity to collagen
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DOI：
10.1016/j.bbrc.2015.12.028
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发表时间：
2016-01-15
影响因子：
3.1
通讯作者：
Nagata, Kazuhiro
中科院分区：
文献类型：
--
作者：
Ito, Shinya;Nagata, Kazuhiro
成骨不全（OI）是一种遗传性疾病，其特征是骨骼脆弱。大多数OI病例是由I型胶原结构或合成缺陷引起的。胶原蛋白特异性分子伴侣Hsp 47（特别是L78 P和L326 P）的突变会导致OI，但这些突变体尚未完全表征。在这里，我们发现这两个Hsp 47突变体的结构不稳定，形成高分子量的复合物。它们被泛素-蛋白酶体系统降解，并且突变体的胶原结合能力显著低于野生型。虽然化学伴侣4-PBA部分恢复了Hsp 47 OI突变体的溶解性，但Hsp 47的胶原结合活性没有改善。(C)2015 Elsevier Inc. All rights reserved.
Osteogenesis imperfecta (OI) is a genetic disorder characterized by fragile bones. Most OI cases are caused by defects in type I collagen structure or synthesis. Mutations in collagen specific molecular chaperone Hsp47, specifically L78P and L326P, lead to OI, yet these mutants are not fully characterized. Here, we found that both Hsp47 mutants were structurally unstable and formed high molecular weight complexes. They were degraded by the ubiquitin-proteasome system, and the collagen-binding ability of the mutants was significantly lower than that of the wild type. Although the chemical chaperone 4-PBA partially restores the solubility of the Hsp47 OI mutants, collagen-binding activity of Hsp47 was not improved. (C) 2015 Elsevier Inc. All rights reserved.