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Title: Distinctive Properties of the Nuclear Localization Signals of Inner Nuclear Membrane Proteins Heh1 and Heh2

Abstract

Targeting of ER-synthesized membrane proteins to the inner nuclear membrane (INM) has long been explained by the diffusion-retention model. However, several INM proteins contain non-classical nuclear localization signal (NLS) sequences, which, in a few instances, have been shown to promote importin α/β- and Ran-dependent translocation to the INM. Here, using structural and biochemical methods, we show that yeast INM proteins Heh2 and Src1/Heh1 contain bipartite import sequences that associate intimately with the minor NLS-binding pocket of yeast importin α and unlike classical NLSs efficiently displace the IBB domain in the absence of importin β. In vivo, the intimate interactions at the minor NLS-binding pocket make the h2NLS highly efficient at recruiting importin α at the ER and drive INM localization of endogenous Heh2. Thus, h1/h2NLSs delineate a novel class of super-potent, IBB-like membrane protein NLSs, distinct from classical NLSs found in soluble cargos and of general interest in biology.

Authors:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1354337
Report Number(s):
BNL-112853-2016-JA
Journal ID: ISSN 0969-2126
DOE Contract Number:  
SC00112704
Resource Type:
Journal Article
Journal Name:
Structure
Additional Journal Information:
Journal Volume: 23; Journal Issue: 7; Journal ID: ISSN 0969-2126
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES

Citation Formats

Lokareddy, Ravi K., Hapsari, Rizqiya A., van Rheenen, Mathilde, Pumroy, Ruth A., Bhardwaj, Anshul, Steen, Anton, Veenhoff, Liesbeth M., and Cingolani, Gino. Distinctive Properties of the Nuclear Localization Signals of Inner Nuclear Membrane Proteins Heh1 and Heh2. United States: N. p., 2015. Web. doi:10.1016/j.str.2015.04.017.
Lokareddy, Ravi K., Hapsari, Rizqiya A., van Rheenen, Mathilde, Pumroy, Ruth A., Bhardwaj, Anshul, Steen, Anton, Veenhoff, Liesbeth M., & Cingolani, Gino. Distinctive Properties of the Nuclear Localization Signals of Inner Nuclear Membrane Proteins Heh1 and Heh2. United States. doi:10.1016/j.str.2015.04.017.
Lokareddy, Ravi K., Hapsari, Rizqiya A., van Rheenen, Mathilde, Pumroy, Ruth A., Bhardwaj, Anshul, Steen, Anton, Veenhoff, Liesbeth M., and Cingolani, Gino. Thu . "Distinctive Properties of the Nuclear Localization Signals of Inner Nuclear Membrane Proteins Heh1 and Heh2". United States. doi:10.1016/j.str.2015.04.017.
@article{osti_1354337,
title = {Distinctive Properties of the Nuclear Localization Signals of Inner Nuclear Membrane Proteins Heh1 and Heh2},
author = {Lokareddy, Ravi K. and Hapsari, Rizqiya A. and van Rheenen, Mathilde and Pumroy, Ruth A. and Bhardwaj, Anshul and Steen, Anton and Veenhoff, Liesbeth M. and Cingolani, Gino},
abstractNote = {Targeting of ER-synthesized membrane proteins to the inner nuclear membrane (INM) has long been explained by the diffusion-retention model. However, several INM proteins contain non-classical nuclear localization signal (NLS) sequences, which, in a few instances, have been shown to promote importin α/β- and Ran-dependent translocation to the INM. Here, using structural and biochemical methods, we show that yeast INM proteins Heh2 and Src1/Heh1 contain bipartite import sequences that associate intimately with the minor NLS-binding pocket of yeast importin α and unlike classical NLSs efficiently displace the IBB domain in the absence of importin β. In vivo, the intimate interactions at the minor NLS-binding pocket make the h2NLS highly efficient at recruiting importin α at the ER and drive INM localization of endogenous Heh2. Thus, h1/h2NLSs delineate a novel class of super-potent, IBB-like membrane protein NLSs, distinct from classical NLSs found in soluble cargos and of general interest in biology.},
doi = {10.1016/j.str.2015.04.017},
journal = {Structure},
issn = {0969-2126},
number = 7,
volume = 23,
place = {United States},
year = {2015},
month = {6}
}