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2025年5月3日 星期六
农业生物技术学报  2019, Vol. 27 Issue (6): 1051-1061    DOI: 10.3969/j.issn.1674-7968.2019.06.011
  研究论文与报告 本期目录 | 过刊浏览 | 高级检索 |
小鼠肌肉生长抑制素Y309和C310位点缺失突变对蛋白结构的影响
陈晨, 朱琳, 周新宇, 白春玲, 郑重, 魏著英*, 李光鹏
内蒙古大学 省部共建草原家畜生殖调控与繁育国家重点实验室,呼和浩特 010070
The Effect of Mice (Mus musculus) Myostatin Y309 and C310 Deletions on Protein Structure
CHEN Chen, ZHU Lin, ZHOU Xin-Yu, BAI Chun-Ling, ZHENG Zhong, WEI Zhu-Ying*, LI Guang-Peng
State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, China
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摘要 肌肉生长抑制素(myostatin, MSTN)又名生长分化因子8 (growth-differentiation factor 8, GDF-8),是转化生长因子-β(transforming growth factor-β, TGF-β)家族成员之一,广泛参与机体生长调控过程。作为肌肉生长的负调控因子,MSTN基因突变会造成肌细胞过度增殖、肌纤维数量增加和肌纤维肥大。本研究通过测序技术及生物信息学方法,对小鼠(Mus musculus) MSTN基因Y309和C310位点缺失突变前后编码蛋白的多级结构及其功能进行预测分析。结果表明,MSTN基因突变小鼠第3外显子nt 175~180发生缺失突变,肌肉组织中MSTN基因mRNA表达量减少,MSTN蛋白表达量也减少,MSTN蛋白受体激活素型受体基因(activin typeⅡreceptor, ActR2b)表达量减少,与肌肉发育相关的成肌决定因子基因(myogenin determination, MyoD),生肌决定因子5基因(myogenic factor 5, Myf5)以及肌细胞生成素基因(myogenin, Myog)的表达量发生显著上调,表现出肌肉肥大的表型。分析突变后的MSTN蛋白结构发现,缺失Y(309)和C(310)位点两个氨基酸破坏了MSTN成熟肽的二硫键,β延伸链延长,蛋白结构改变。蛋白功能预测表明,在MSTN突变蛋白内缺失了一个蛋白结合位点,从而影响了其与受体的结合。本研究表明,小鼠MSTN第3外显子nt 175~180是影响MSTN蛋白功能的核心序列,缺失突变后会产生肌肉肥大的表型,为研究MSTN基因功能提供了良好的小鼠模型。
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关键词 MSTN基因敲除蛋白质结构生物信息学    
Abstract:Myostatin (MSTN), also known as GDF-8 (growth-differentiation factor 8), is a member of the transforming growth factor-beta (TGF-β) super-family, which participates in various process of body growth regulation. As a negative regulatory of muscle growth, its mutation will lead to the excessive proliferation of muscle cells and muscle hypertrophy. To study how MSTN mutation affect its protein structure and biology functions, the multi-level structure and function changes of MSTN were predicted and analyzed by bioinformatics methods, based on our MSTN gene knock-out mice (Mus musculus). The results showed that the nt 175~180 sequence in the third exon of the MSTN gene was missing, the expression level of the MSTN decreased which led to deprived the MSTN protein in muscle, the expression level of myogenin determination gene (Myod), myogenic factor 5 gene (Myf5) and myogenin gene (Myog) increased significantly, activin typeⅡreceptor b3 gene (ActR2b3), the receptor protein of the MSTN decreased and the muscle hypertrophy. Analysis of the deletion mutation MSTN protein structure, it lost the Y (309) and C(310) amino acids, which elongated the beta pleated sheet and changed the protein structure. The functional prediction result showed that, the mutant MTSN protein of these mice lost a protein bonding site, which reduced its bonding capability to the receptor and impaired its biological functions. This study showed that the third exon nt 175~180 of MSTN in mice was the core sequence that affected the function of MSTN protein, and resulted in the muscle hypertrophy phenotype, which would provide a good mouse model for studying the function of MSTN gene.
Key wordsMSTN    Gene knockout    Protein structure    Bioinformatics
收稿日期: 2018-11-27     
ZTFLH:  S185  
基金资助:国家转基因生物新品种培育重大专项(No. 2016ZX08007-002)
通讯作者: zywei@imu.edu.cn   
引用本文:   
陈晨, 朱琳, 周新宇, 白春玲, 郑重, 魏著英, 李光鹏. 小鼠肌肉生长抑制素Y309和C310位点缺失突变对蛋白结构的影响[J]. 农业生物技术学报, 2019, 27(6): 1051-1061.
CHEN Chen ZHU Lin ZHOU Xin-Yu BAI Chun-Ling ZHENG Zhong WEI Zhu-Ying, LI Guang-Peng. The Effect of Mice (Mus musculus) Myostatin Y309 and C310 Deletions on Protein Structure. 农业生物技术学报, 2019, 27(6): 1051-1061.
链接本文:  
http://journal05.magtech.org.cn/Jwk_ny/CN/10.3969/j.issn.1674-7968.2019.06.011     或     http://journal05.magtech.org.cn/Jwk_ny/CN/Y2019/V27/I6/1051
 
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