Both the PH domain and N-terminal region of oxysterol-binding protein related protein 8S are required for localization to PM-ER contact sites

Minhyoung Lee; Gregory D. Fairn

doi:10.1016/j.bbrc.2018.01.138

Both the PH domain and N-terminal region of oxysterol-binding protein related protein 8S are required for localization to PM-ER contact sites

Minhyoung Lee, Gregory D. Fairn

Résultat de recherche: Article › examen par les pairs

11 Citations (Scopus)

Résumé

Oxysterol-binding protein-related proteins are implicated in the sensing and transporting lipids at the membrane contact sites. One of the members of the mammalian ORP family, ORP8, is thought to transport lipids through directly tethering both ER and PM membranes. Targeting to PM is thought to be mediated by N-terminal pleckstrin homology domain via binding to phosphoinositides. Sequence alignments and NMR structural determination revealed that the PH domain of ORP8 is atypical and contains an insertion of 20 amino acids in an unstructured loop region that may potentially block interactions with ligands. Using standard lipid-protein overlay assays or liposomal binding assays we could not detect binding of a recombinant version of the PH domain. Examination of a series of deletion constructs demonstrated that both the N-terminal polybasic region and the PH domain are required for proper targeting of the short splice variant ORP8S to the PM-ER contact site in Chinese hamster ovary cells.

Langue d'origine	English
Pages (de-à)	1088-1094
Nombre de pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	496
Numéro de publication	4
DOI	https://doi.org/10.1016/j.bbrc.2018.01.138
Statut de publication	Published - févr. 19 2018
Publié à l'externe	Oui

Note bibliographique

Funding Information:
This work was supported in part by Operating Grant MOP-133656 and a New Investigator Award from the Canadian Institutes of Health Research (CIHR) and an Early Researcher Award from the Government of Ontario . M.L. is supported in part by scholarships from the Li Ka Shing Knowledge Institute and a Government of Ontario Graduate Scholarship. The authors declare that they have no conflicts of interest with the contents of this article.

Publisher Copyright:
© 2018

ASJC Scopus Subject Areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

Accès au document

10.1016/j.bbrc.2018.01.138

Autres fichiers et liens

Citer

@article{451d74a266f84543ab745d64a5c02002,

title = "Both the PH domain and N-terminal region of oxysterol-binding protein related protein 8S are required for localization to PM-ER contact sites",

abstract = "Oxysterol-binding protein-related proteins are implicated in the sensing and transporting lipids at the membrane contact sites. One of the members of the mammalian ORP family, ORP8, is thought to transport lipids through directly tethering both ER and PM membranes. Targeting to PM is thought to be mediated by N-terminal pleckstrin homology domain via binding to phosphoinositides. Sequence alignments and NMR structural determination revealed that the PH domain of ORP8 is atypical and contains an insertion of 20 amino acids in an unstructured loop region that may potentially block interactions with ligands. Using standard lipid-protein overlay assays or liposomal binding assays we could not detect binding of a recombinant version of the PH domain. Examination of a series of deletion constructs demonstrated that both the N-terminal polybasic region and the PH domain are required for proper targeting of the short splice variant ORP8S to the PM-ER contact site in Chinese hamster ovary cells.",

author = "Minhyoung Lee and Fairn, {Gregory D.}",

note = "Funding Information: This work was supported in part by Operating Grant MOP-133656 and a New Investigator Award from the Canadian Institutes of Health Research (CIHR) and an Early Researcher Award from the Government of Ontario . M.L. is supported in part by scholarships from the Li Ka Shing Knowledge Institute and a Government of Ontario Graduate Scholarship. The authors declare that they have no conflicts of interest with the contents of this article. Publisher Copyright: {\textcopyright} 2018",

year = "2018",

month = feb,

day = "19",

doi = "10.1016/j.bbrc.2018.01.138",

language = "English",

volume = "496",

pages = "1088--1094",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Academic Press Inc.",

number = "4",

}

TY - JOUR

T1 - Both the PH domain and N-terminal region of oxysterol-binding protein related protein 8S are required for localization to PM-ER contact sites

AU - Lee, Minhyoung

AU - Fairn, Gregory D.

N1 - Funding Information: This work was supported in part by Operating Grant MOP-133656 and a New Investigator Award from the Canadian Institutes of Health Research (CIHR) and an Early Researcher Award from the Government of Ontario . M.L. is supported in part by scholarships from the Li Ka Shing Knowledge Institute and a Government of Ontario Graduate Scholarship. The authors declare that they have no conflicts of interest with the contents of this article. Publisher Copyright: © 2018

PY - 2018/2/19

Y1 - 2018/2/19

N2 - Oxysterol-binding protein-related proteins are implicated in the sensing and transporting lipids at the membrane contact sites. One of the members of the mammalian ORP family, ORP8, is thought to transport lipids through directly tethering both ER and PM membranes. Targeting to PM is thought to be mediated by N-terminal pleckstrin homology domain via binding to phosphoinositides. Sequence alignments and NMR structural determination revealed that the PH domain of ORP8 is atypical and contains an insertion of 20 amino acids in an unstructured loop region that may potentially block interactions with ligands. Using standard lipid-protein overlay assays or liposomal binding assays we could not detect binding of a recombinant version of the PH domain. Examination of a series of deletion constructs demonstrated that both the N-terminal polybasic region and the PH domain are required for proper targeting of the short splice variant ORP8S to the PM-ER contact site in Chinese hamster ovary cells.

AB - Oxysterol-binding protein-related proteins are implicated in the sensing and transporting lipids at the membrane contact sites. One of the members of the mammalian ORP family, ORP8, is thought to transport lipids through directly tethering both ER and PM membranes. Targeting to PM is thought to be mediated by N-terminal pleckstrin homology domain via binding to phosphoinositides. Sequence alignments and NMR structural determination revealed that the PH domain of ORP8 is atypical and contains an insertion of 20 amino acids in an unstructured loop region that may potentially block interactions with ligands. Using standard lipid-protein overlay assays or liposomal binding assays we could not detect binding of a recombinant version of the PH domain. Examination of a series of deletion constructs demonstrated that both the N-terminal polybasic region and the PH domain are required for proper targeting of the short splice variant ORP8S to the PM-ER contact site in Chinese hamster ovary cells.

UR - http://www.scopus.com/inward/record.url?scp=85041931727&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041931727&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2018.01.138

DO - 10.1016/j.bbrc.2018.01.138

M3 - Article

C2 - 29409900

AN - SCOPUS:85041931727

SN - 0006-291X

VL - 496

SP - 1088

EP - 1094

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -

Both the PH domain and N-terminal region of oxysterol-binding protein related protein 8S are required for localization to PM-ER contact sites

Résumé

Note bibliographique

ASJC Scopus Subject Areas

PubMed: MeSH publication types

Accès au document

Autres fichiers et liens

Empreinte numérique

Citer