The importance of N-glycosylation on β3 integrin ligand binding and conformational regulation

Abstract N-glycosylations can regulate the adhesive function of integrins. Great variations in both the number and distribution of N-glycosylation sites are found in the 18 α and 8 β integrin subunits. Crystal structures of αIIbβ3 and αVβ3 have resolved the precise structural location of each N-glyc...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xiulei Cai, Aye Myat Myat Thinn, Zhengli Wang, Hu Shan, Jieqing Zhu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/431d93d9f57341798f20c2a6e6140743
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:431d93d9f57341798f20c2a6e6140743
record_format	dspace
spelling	oai:doaj.org-article:431d93d9f57341798f20c2a6e61407432021-12-02T11:40:24ZThe importance of N-glycosylation on β3 integrin ligand binding and conformational regulation10.1038/s41598-017-04844-w2045-2322https://doaj.org/article/431d93d9f57341798f20c2a6e61407432017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04844-whttps://doaj.org/toc/2045-2322Abstract N-glycosylations can regulate the adhesive function of integrins. Great variations in both the number and distribution of N-glycosylation sites are found in the 18 α and 8 β integrin subunits. Crystal structures of αIIbβ3 and αVβ3 have resolved the precise structural location of each N-glycan site, but the structural consequences of individual N-glycan site on integrin activation remain unclear. By site-directed mutagenesis and structure-guided analyses, we dissected the function of individual N-glycan sites in β3 integrin activation. We found that the N-glycan site, β3-N320 at the headpiece and leg domain interface positively regulates αIIbβ3 but not αVβ3 activation. The β3-N559 N-glycan at the β3-I-EGF3 and αIIb-calf-1 domain interface, and the β3-N654 N-glycan at the β3-β-tail and αIIb-calf-2 domain interface positively regulate the activation of both αIIbβ3 and αVβ3 integrins. In contrast, removal of the β3-N371 N-glycan near the β3 hybrid and I-EGF3 interface, or the β3-N452 N-glycan at the I-EGF1 domain rendered β3 integrin more active than the wild type. We identified one unique N-glycan at the βI domain of β1 subunit that negatively regulates α5β1 activation. Our study suggests that the bulky N-glycans influence the large-scale conformational rearrangement by potentially stabilizing or destabilizing the domain interfaces of integrin.Xiulei CaiAye Myat Myat ThinnZhengli WangHu ShanJieqing ZhuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiulei Cai Aye Myat Myat Thinn Zhengli Wang Hu Shan Jieqing Zhu The importance of N-glycosylation on β3 integrin ligand binding and conformational regulation
description	Abstract N-glycosylations can regulate the adhesive function of integrins. Great variations in both the number and distribution of N-glycosylation sites are found in the 18 α and 8 β integrin subunits. Crystal structures of αIIbβ3 and αVβ3 have resolved the precise structural location of each N-glycan site, but the structural consequences of individual N-glycan site on integrin activation remain unclear. By site-directed mutagenesis and structure-guided analyses, we dissected the function of individual N-glycan sites in β3 integrin activation. We found that the N-glycan site, β3-N320 at the headpiece and leg domain interface positively regulates αIIbβ3 but not αVβ3 activation. The β3-N559 N-glycan at the β3-I-EGF3 and αIIb-calf-1 domain interface, and the β3-N654 N-glycan at the β3-β-tail and αIIb-calf-2 domain interface positively regulate the activation of both αIIbβ3 and αVβ3 integrins. In contrast, removal of the β3-N371 N-glycan near the β3 hybrid and I-EGF3 interface, or the β3-N452 N-glycan at the I-EGF1 domain rendered β3 integrin more active than the wild type. We identified one unique N-glycan at the βI domain of β1 subunit that negatively regulates α5β1 activation. Our study suggests that the bulky N-glycans influence the large-scale conformational rearrangement by potentially stabilizing or destabilizing the domain interfaces of integrin.
format	article
author	Xiulei Cai Aye Myat Myat Thinn Zhengli Wang Hu Shan Jieqing Zhu
author_facet	Xiulei Cai Aye Myat Myat Thinn Zhengli Wang Hu Shan Jieqing Zhu
author_sort	Xiulei Cai
title	The importance of N-glycosylation on β3 integrin ligand binding and conformational regulation
title_short	The importance of N-glycosylation on β3 integrin ligand binding and conformational regulation
title_full	The importance of N-glycosylation on β3 integrin ligand binding and conformational regulation
title_fullStr	The importance of N-glycosylation on β3 integrin ligand binding and conformational regulation
title_full_unstemmed	The importance of N-glycosylation on β3 integrin ligand binding and conformational regulation
title_sort	importance of n-glycosylation on β3 integrin ligand binding and conformational regulation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/431d93d9f57341798f20c2a6e6140743
work_keys_str_mv	AT xiuleicai theimportanceofnglycosylationonb3integrinligandbindingandconformationalregulation AT ayemyatmyatthinn theimportanceofnglycosylationonb3integrinligandbindingandconformationalregulation AT zhengliwang theimportanceofnglycosylationonb3integrinligandbindingandconformationalregulation AT hushan theimportanceofnglycosylationonb3integrinligandbindingandconformationalregulation AT jieqingzhu theimportanceofnglycosylationonb3integrinligandbindingandconformationalregulation AT xiuleicai importanceofnglycosylationonb3integrinligandbindingandconformationalregulation AT ayemyatmyatthinn importanceofnglycosylationonb3integrinligandbindingandconformationalregulation AT zhengliwang importanceofnglycosylationonb3integrinligandbindingandconformationalregulation AT hushan importanceofnglycosylationonb3integrinligandbindingandconformationalregulation AT jieqingzhu importanceofnglycosylationonb3integrinligandbindingandconformationalregulation
_version_	1718395638339600384

The importance of N-glycosylation on β3 integrin ligand binding and conformational regulation

Ejemplares similares