The sequence determinant causing different folding behaviors of insulin and insulin-like growth factor-1

	The sequence determinant causing different folding behaviors of insulin and insulin-like growth factor-1
	Huang, QL; Zhao, J; Tang, YH; Shao, SQ; Xu, GJ; Feng, YM
刊名	BIOCHEMISTRY
	2007
卷号	46 期号:1 页码:218-224
通讯作者	Feng, YM (reprint author), Chinese Acad Sci, Inst Biochem & Cell Biol, SIBS, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,fengym@sunm.shcnc.ac.cn
英文摘要	Although insulin and insulin-like growth factor-1 (IGF-1) belong to the insulin superfamily and share highly homologous sequences, similar tertiary structure, and a common ancestor molecule, amphioxus insulin-like peptide, they have different folding behaviors: IGF-1 folds into two thermodynamically stable tertiary structures (native and swap forms), while insulin folds into one unique stable structure. To further understand which part of the sequence determines their different folding behavior, based on previous reports from the laboratory, two peptide models, [B9A][1-4]porcine insulin precursor (PIP) and [B10E][1-4]PIP, were constructed. The plasmids encoding the peptides were transformed into yeast cells for expression of the peptides; the results showed that the former peptide was expressed as single component, while the latter was expressed as a mixture of two components (isomer 1 and isomer 2). The expression results together with studies of circular dichoism, disulfide rearrangement, and refolding lead us to deduce that isomer 1 corresponds to the swap form and the isomer 2 corresponds to the native form. We further demonstrate that the sequence 1-4 plus B9 of IGF-1 B-domain can make PIP fold into two structures, while sequence 1-5 of insulin B-chain can make IGF-1 fold into one unique structure. In other words, it is the IGF-1 B-domain sequence that 1-4 allows IGF-1 folding into two thermodynamically stable tertiary structures; this sequence plus its residue B9E can change PIP folding behavior from folding into one unique structure to two thermodynamically stable structures, like that of IGF-1.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	B-CHAIN/DOMAIN ; IGF-I ; DISULFIDE ; INSULIN-LIKE-GROWTH-FACTOR-1 ; AMPHIOXUS ; PEPTIDE ; EVOLUTION ; PROTEIN ; VITRO ; PRECURSOR
收录类别	SCI
语种	英语
WOS记录号	WOS:000243157300023
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1506]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Huang, QL,Zhao, J,Tang, YH,et al. The sequence determinant causing different folding behaviors of insulin and insulin-like growth factor-1[J]. BIOCHEMISTRY,2007,46(1):218-224.
APA	Huang, QL,Zhao, J,Tang, YH,Shao, SQ,Xu, GJ,&Feng, YM.(2007).The sequence determinant causing different folding behaviors of insulin and insulin-like growth factor-1.BIOCHEMISTRY,46(1),218-224.
MLA	Huang, QL,et al."The sequence determinant causing different folding behaviors of insulin and insulin-like growth factor-1".BIOCHEMISTRY 46.1(2007):218-224.