Flexible and Extended Linker Domains Support Efficient Targeting of Heh2 to the Inner Nuclear Membrane.


Journal

Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697

Informations de publication

Date de publication:
04 02 2020
Historique:
received: 08 04 2019
revised: 09 08 2019
accepted: 08 11 2019
pubmed: 7 12 2019
medline: 30 4 2021
entrez: 7 12 2019
Statut: ppublish

Résumé

The nuclear pore complex (NPC) is embedded in the nuclear envelope and forms the main gateway to the nuclear interior including the inner nuclear membrane (INM). Two INM proteins in yeast are selectively imported. Their sorting signals consist of a nuclear localization signal, separated from the transmembrane domain by a long intrinsically disordered (ID) linker. We used computational models to predict the dynamic conformations of ID linkers and analyzed the INM targeting efficiency of proteins with linker regions with altered Stokes radii and decreased flexibilities. We find that flexibility, Stokes radius, and the frequency at which the linkers are at an extended end-to-end distance larger than 25 nm are good predictors for the targeting of the proteins. The data are consistent with a transport mechanism in which INM targeting of Heh2 is dependent on an ID linker that facilitates the crossing of the approximately 25-nm thick NPC scaffold.

Identifiants

pubmed: 31806352
pii: S0969-2126(19)30387-9
doi: 10.1016/j.str.2019.11.003
pii:
doi:

Substances chimiques

Heh2 protein, S cerevisiae 0
Membrane Proteins 0
Nuclear Proteins 0
Protein Sorting Signals 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

185-195.e5

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

Auteurs

Irina L Rempel (IL)

European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, Netherlands.

Petra Popken (P)

European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, Netherlands; Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, Groningen 9747 AG, The Netherlands; Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, Groningen 9747 AG, The Netherlands.

Ali Ghavami (A)

Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, Groningen 9747 AG, The Netherlands.

Ankur Mishra (A)

Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, Groningen 9747 AG, The Netherlands.

Rizqiya A Hapsari (RA)

European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, Netherlands.

Anouk H G Wolters (AHG)

Department of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, Netherlands.

Annemiek C Veldsink (AC)

European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, Netherlands.

Marindy Klaassens (M)

European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, Netherlands.

Anne C Meinema (AC)

Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, Groningen 9747 AG, The Netherlands.

Bert Poolman (B)

Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, Groningen 9747 AG, The Netherlands; Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, Groningen 9747 AG, The Netherlands.

Ben N G Giepmans (BNG)

Department of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, Netherlands.

Patrick R Onck (PR)

Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, Groningen 9747 AG, The Netherlands. Electronic address: p.r.onck@rug.nl.

Anton Steen (A)

European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, Netherlands. Electronic address: a.steen@umcg.nl.

Liesbeth M Veenhoff (LM)

European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, Netherlands. Electronic address: l.m.veenhoff@rug.nl.

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Classifications MeSH