Effects of cataract-causing mutations W59C and W151C on βB2-crystallin structure, stability and folding
Effects of cataract-causing mutations W59C and W151C on βB2-crystallin structure, stability and folding
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引起白内障的突变 W59C 和 W151C 对 β B2 晶状体蛋白结构、稳定性和折叠的影响
DOI：
10.1016/j.ijbiomac.2017.05.109
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发表时间：
2017-10-01
影响因子：
8.2
通讯作者：
Yan, Yong-Bin
中科院分区：
文献类型：
--
作者：
Zhao, Wei-Jie;Xu, Jia;Yan, Yong-Bin
β/γ-晶体蛋白是脊椎动物透镜中的主要结构蛋白，具有终身稳定性以维持透镜透明度，其一级序列和三级结构具有高度相似性。四个保守的Trp残基已被证明是重要的γ-晶体蛋白的结构，稳定性和保护免受紫外线照射，而他们的作用在β-晶体蛋白仍然难以捉摸。在此，我们发现，两个先天性白内障引起的突变，W59 C和W151 C，显着降低β B2-晶状体蛋白的溶解度和稳定性，对热和盐酸胍诱导的变性。这两种突变蛋白在试管中受紫外光照射或在细胞中外源表达时易于形成聚集体。虽然W59和W151在β/γ-晶状体蛋白结构域中结构相同，但用Cys取代它们导致对β B2-晶状体蛋白稳定性的不同影响。我们的研究结果表明，保守的色氨酸残基可能发挥更重要的作用，在正确的折叠和结构完整性的β-晶体蛋白结构域比γ-晶体蛋白。(C)2017 Elsevier B. V.版权所有。
beta/gamma-Crystallins, the predominant structural proteins in vertebrate lens with lifelong stability to maintain lens transparency, share a high similarity in their primary sequences and tertiary structures. Four conserved Trp residues have been shown to be important to gamma-crystallin structure, stability and protection against UV irradiation, whereas their roles in beta-crystallins remain elusive. Herein we found that two congenital cataract-causing mutations, W59C and W151C, dramatically decreased beta B2-crystallin solubility and stability against thermal and guanidine hydrochloride-induced denaturation. The two mutated proteins were prone to form aggregates when irradiated by UV light in the tubes or exogenously expressed in the cells. Although W59 and W151 are structurally identical in beta/gamma-crystallin domains, substituting them by Cys led to dissimilar influences on beta B2-crystallin stability. Our results suggested that the conserved Trp residues might play a more crucial role in the correct folding and structural integrity of beta-crystallin domains than in gamma-crystallins. (C) 2017 Elsevier B.V. All rights reserved.