干旱区生态环境知识资源中心(Arid): DHH pathogenic variants involved in 46,XY disorders of sex development differentially impact protein self-cleavage and structural conformation

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DOI	10.1007/s00439-020-02189-5
	DHH pathogenic variants involved in 46,XY disorders of sex development differentially impact protein self-cleavage and structural conformation
	Elzaiat, Maeva 1; Flatters, Delphine 2; Carolina Sierra-Diaz, Diana 3; Legois, Berangere 1; Laissue, Paul 3,4; Veitia, Reiner A.1,5
通讯作者	Veitia, Reiner A.
来源期刊	HUMAN GENETICS
ISSN	0340-6717
EISSN	1432-1203
出版年	2020
卷号	139 期号:11 页码:1455-1470
英文摘要	In humans, pathogenic variants in the DHH gene underlie cases of 46,XY gonadal dysgenesis. DHH is part of the Hedgehog family of proteins, which require extensive processing, including self-cleavage of the precursor for efficient signalling. In our work, we have assessed the effect of several human DHH pathogenic variants involved in recessive complete or partial gonadal dysgenesis, on protein processing and sub-cellular localization. We found that a subset of variants was unable to perform self-cleavage, which correlated albeit not perfectly with an altered subcellular localization of the resulting proteins. For the processing-proficient variants, we used structural modelling tools and molecular dynamic (MD) simulations to predict the potential impact of the variants on protein conformation and/or interaction with partners. Our study contributes to a better understanding of the molecular mechanisms involved in DHH dysfunction leading to 46,XY disorders of sex development.
类型	Article
语种	英语
国家	France ; Colombia
收录类别	SCI-E
WOS记录号	WOS:000538506200001
WOS关键词	DESERT-HEDGEHOG GENE ; GONADAL-DYSGENESIS ; SONIC HEDGEHOG ; MUTATIONS ; INSIGHTS ; TESTIS ; FETAL ; FORM ; BOC
WOS类目	Genetics & Heredity
WOS研究方向	Genetics & Heredity
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/318777
作者单位	1.Univ Paris Diderot, CNRS, UMR7592, Inst Jacques Monod, 15 Rue Helene Brion, F-75013 Paris, France; 2.Univ Paris, INSERM, UMR 8251, BFA,ERL U1133,CNRS, F-75013 Paris, France; 3.El Rosario Univ, Fac Med, Genet Grp, Bogota, Colombia; 4.BIOPAS Grp, Biopas Labs, Bogota, Colombia; 5.Univ Paris Saclay, Inst Biol Francois Jacob, DRF, CEA, Fontenay Aux Roses, France
推荐引用方式 GB/T 7714	Elzaiat, Maeva,Flatters, Delphine,Carolina Sierra-Diaz, Diana,et al. DHH pathogenic variants involved in 46,XY disorders of sex development differentially impact protein self-cleavage and structural conformation[J],2020,139(11):1455-1470.
APA	Elzaiat, Maeva,Flatters, Delphine,Carolina Sierra-Diaz, Diana,Legois, Berangere,Laissue, Paul,&Veitia, Reiner A..(2020).DHH pathogenic variants involved in 46,XY disorders of sex development differentially impact protein self-cleavage and structural conformation.HUMAN GENETICS,139(11),1455-1470.
MLA	Elzaiat, Maeva,et al."DHH pathogenic variants involved in 46,XY disorders of sex development differentially impact protein self-cleavage and structural conformation".HUMAN GENETICS 139.11(2020):1455-1470.