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Structure. 2015 Jul 7;23(7):1305-1316. doi: 10.1016/j.str.2015.04.017. Epub 2015 Jun 4.

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

Author information

1
Dept. of Biochemistry and Molecular Biology, Thomas Jefferson University, 233 South 10 Street, Philadelphia, PA 19107, USA.
2
European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
3
Zernike Institute for Advanced Materials, Department of Biochemistry, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, Netherlands.
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Contributed equally

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.

PMID:
26051712
PMCID:
PMC4768490
DOI:
10.1016/j.str.2015.04.017
[Indexed for MEDLINE]
Free PMC Article

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