The crystal structure of human Rogdi provides insight into the causes of Kohlschutter-Tönz Syndrome

Abstract Kohlschutter-Tönz syndrome (KTS) is a rare autosomal-recessive disorder of childhood onset characterized by global developmental delay, spasticity, epilepsy, and amelogenesis imperfecta. Rogdi, an essential protein, is highly conserved across metazoans, and mutations in Rogdi are linked to...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hakbong Lee, Hanbin Jeong, Joonho Choe, Youngsoo Jun, Chunghun Lim, Changwook Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c8a95ac736af4d388d56fe11595dcb96
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c8a95ac736af4d388d56fe11595dcb96
record_format	dspace
spelling	oai:doaj.org-article:c8a95ac736af4d388d56fe11595dcb962021-12-02T15:05:32ZThe crystal structure of human Rogdi provides insight into the causes of Kohlschutter-Tönz Syndrome10.1038/s41598-017-04120-x2045-2322https://doaj.org/article/c8a95ac736af4d388d56fe11595dcb962017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04120-xhttps://doaj.org/toc/2045-2322Abstract Kohlschutter-Tönz syndrome (KTS) is a rare autosomal-recessive disorder of childhood onset characterized by global developmental delay, spasticity, epilepsy, and amelogenesis imperfecta. Rogdi, an essential protein, is highly conserved across metazoans, and mutations in Rogdi are linked to KTS. However, how certain mutations in Rogdi abolish its physiological functions and cause KTS is not known. In this study, we determined the crystal structure of human Rogdi protein at atomic resolution. Rogdi forms a novel elongated curved structure comprising the α domain, a leucine-zipper-like four-helix bundle, and a characteristic β-sheet domain. Within the α domain, the N-terminal H1 helix (residues 19–45) pairs with the C-terminal H6 helix (residues 252–287) in an antiparallel manner, indicating that the integrity of the four-helix bundle requires both N- and C-terminal residues. The crystal structure, in conjunction with biochemical data, indicates that the α domain might undergo a conformational change and provide a structural platform for protein–protein interactions. Disruption of the four-helix bundle by mutation results in significant destabilization of the structure. This study provides structural insights into how certain mutations in Rogdi affect its structure and cause KTS, which has important implications for the development of pharmaceutical agents against this debilitating neurological disease.Hakbong LeeHanbin JeongJoonho ChoeYoungsoo JunChunghun LimChangwook LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hakbong Lee Hanbin Jeong Joonho Choe Youngsoo Jun Chunghun Lim Changwook Lee The crystal structure of human Rogdi provides insight into the causes of Kohlschutter-Tönz Syndrome
description	Abstract Kohlschutter-Tönz syndrome (KTS) is a rare autosomal-recessive disorder of childhood onset characterized by global developmental delay, spasticity, epilepsy, and amelogenesis imperfecta. Rogdi, an essential protein, is highly conserved across metazoans, and mutations in Rogdi are linked to KTS. However, how certain mutations in Rogdi abolish its physiological functions and cause KTS is not known. In this study, we determined the crystal structure of human Rogdi protein at atomic resolution. Rogdi forms a novel elongated curved structure comprising the α domain, a leucine-zipper-like four-helix bundle, and a characteristic β-sheet domain. Within the α domain, the N-terminal H1 helix (residues 19–45) pairs with the C-terminal H6 helix (residues 252–287) in an antiparallel manner, indicating that the integrity of the four-helix bundle requires both N- and C-terminal residues. The crystal structure, in conjunction with biochemical data, indicates that the α domain might undergo a conformational change and provide a structural platform for protein–protein interactions. Disruption of the four-helix bundle by mutation results in significant destabilization of the structure. This study provides structural insights into how certain mutations in Rogdi affect its structure and cause KTS, which has important implications for the development of pharmaceutical agents against this debilitating neurological disease.
format	article
author	Hakbong Lee Hanbin Jeong Joonho Choe Youngsoo Jun Chunghun Lim Changwook Lee
author_facet	Hakbong Lee Hanbin Jeong Joonho Choe Youngsoo Jun Chunghun Lim Changwook Lee
author_sort	Hakbong Lee
title	The crystal structure of human Rogdi provides insight into the causes of Kohlschutter-Tönz Syndrome
title_short	The crystal structure of human Rogdi provides insight into the causes of Kohlschutter-Tönz Syndrome
title_full	The crystal structure of human Rogdi provides insight into the causes of Kohlschutter-Tönz Syndrome
title_fullStr	The crystal structure of human Rogdi provides insight into the causes of Kohlschutter-Tönz Syndrome
title_full_unstemmed	The crystal structure of human Rogdi provides insight into the causes of Kohlschutter-Tönz Syndrome
title_sort	crystal structure of human rogdi provides insight into the causes of kohlschutter-tönz syndrome
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c8a95ac736af4d388d56fe11595dcb96
work_keys_str_mv	AT hakbonglee thecrystalstructureofhumanrogdiprovidesinsightintothecausesofkohlschuttertonzsyndrome AT hanbinjeong thecrystalstructureofhumanrogdiprovidesinsightintothecausesofkohlschuttertonzsyndrome AT joonhochoe thecrystalstructureofhumanrogdiprovidesinsightintothecausesofkohlschuttertonzsyndrome AT youngsoojun thecrystalstructureofhumanrogdiprovidesinsightintothecausesofkohlschuttertonzsyndrome AT chunghunlim thecrystalstructureofhumanrogdiprovidesinsightintothecausesofkohlschuttertonzsyndrome AT changwooklee thecrystalstructureofhumanrogdiprovidesinsightintothecausesofkohlschuttertonzsyndrome AT hakbonglee crystalstructureofhumanrogdiprovidesinsightintothecausesofkohlschuttertonzsyndrome AT hanbinjeong crystalstructureofhumanrogdiprovidesinsightintothecausesofkohlschuttertonzsyndrome AT joonhochoe crystalstructureofhumanrogdiprovidesinsightintothecausesofkohlschuttertonzsyndrome AT youngsoojun crystalstructureofhumanrogdiprovidesinsightintothecausesofkohlschuttertonzsyndrome AT chunghunlim crystalstructureofhumanrogdiprovidesinsightintothecausesofkohlschuttertonzsyndrome AT changwooklee crystalstructureofhumanrogdiprovidesinsightintothecausesofkohlschuttertonzsyndrome
_version_	1718388792724815872

The crystal structure of human Rogdi provides insight into the causes of Kohlschutter-Tönz Syndrome

Ejemplares similares