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

Ravi K Lokareddy, Rizqiya A Hapsari, Mathilde van Rheenen, Ruth A Pumroy, Anshul Bhardwaj, Anton Steen, Liesbeth M Veenhoff, Gino Cingolani

Structure (London, England : 1993) 2015 Jul 07

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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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Citation

Ravi K Lokareddy, Rizqiya A Hapsari, Mathilde van Rheenen, Ruth A Pumroy, Anshul Bhardwaj, Anton Steen, Liesbeth M Veenhoff, Gino Cingolani. Distinctive Properties of the Nuclear Localization Signals of Inner Nuclear Membrane Proteins Heh1 and Heh2. Structure (London, England : 1993). 2015 Jul 07;23(7):1305-1316