4PVZ

Structure of yeast importin a bound to the membrane protein Nuclear Localization Signal sequence of INM protein Heh2

Summary for 4PVZ

• Entry DOI: 10.2210/pdb4pvz/pdb
• Related: 1BK5 1EE4 1EE5
• Descriptor: Importin subunit alpha, Inner nuclear membrane protein HEH2 (3 entities in total)
• Functional Keywords: armadillo repeated structure, nuclear import adapter, importin beta, nls-cargos, protein binding
• Biological source: Saccharomyces cerevisiae S288c (Baker's yeast); More
• Cellular location: Cytoplasm, perinuclear region: Q02821; Nucleus inner membrane ; Single-pass membrane protein : Q03281
• Total number of polymer chains: 4
• Total formula weight: 103550.49

Authors

Lokareddy, R.K.,Hapsari, A.R.,van Rheenen, M.,Bhardwaj, A.,Veenhoff, L.M.,Cingolani, C. (deposition date: 2014-03-18, release date: 2015-08-26, Last modification date: 2023-09-20)

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 (2.5 Å)