4XZR

Structure of yeast importin a bound to the membrane protein Nuclear Localization Signal sequence of INM protein Heh1

Summary for 4XZR

• Entry DOI: 10.2210/pdb4xzr/pdb
• Related: 4PVZ
• Descriptor: Inner nuclear membrane protein SRC1, Importin subunit alpha (3 entities in total)
• Functional Keywords: karyopherins; nuclear import; nls; membrane proteins, membrane protein-nuclear protein complex, membrane protein/nuclear protein
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); More
• Total number of polymer chains: 2
• Total formula weight: 53228.45

Authors

Lokareddy, R.K.,Cingolani, G. (deposition date: 2015-02-04, release date: 2015-06-17, Last modification date: 2024-02-28)

Primary citation

Lokareddy, R.K.,Hapsari, R.A.,van Rheenen, M.,Pumroy, R.A.,Bhardwaj, A.,Steen, A.,Veenhoff, L.M.,Cingolani, G.
Distinctive Properties of the Nuclear Localization Signals of Inner Nuclear Membrane Proteins Heh1 and Heh2.
Structure, 23:1305-1316, 2015

PubMed 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.

PubMed: 26051712
DOI: 10.1016/j.str.2015.04.017

Experimental method

X-RAY DIFFRACTION (2.25 Å)