4B18

The crystal structure of human Importin alpha 5 with TERT NLS peptide

Summary for 4B18

• Entry DOI: 10.2210/pdb4b18/pdb
• Related: 2BCK 2JDQ
• Descriptor: IMPORTIN SUBUNIT ALPHA-1, TELOMERASE REVERSE TRANSCRIPTASE (3 entities in total)
• Functional Keywords: transport protein - peptide complex, transport protein / peptide
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm : P52294; Nucleus, nucleolus: O14746
• Total number of polymer chains: 2
• Total formula weight: 51684.03

Authors

Kim, K.L.,Yoo, J.H.,Cho, H.S. (deposition date: 2012-07-08, release date: 2013-09-04, Last modification date: 2023-12-20)

Primary citation

Jeong, S.A.,Kim, K.,Lee, J.H.,Cha, J.S.,Khadka, P.,Cho, H.,Chung, I.K.
Akt-Mediated Phosphorylation Increases the Binding Affinity of Htert for Importin Alpha to Promote Nuclear Translocation.
J.Cell.Sci., 128:2287-, 2015

PubMed Abstract: Telomeres are essential for chromosome integrity and protection, and their maintenance requires the ribonucleoprotein enzyme telomerase. Previously, we have shown that human telomerase reverse transcriptase (hTERT) contains a bipartite nuclear localization signal (NLS; residues 222-240) that is responsible for nuclear import, and that Akt-mediated phosphorylation of residue S227 is important for efficient nuclear import of hTERT. Here, we show that hTERT binds to importin-α proteins through the bipartite NLS and that this heterodimer then forms a complex with importin-β proteins to interact with the nuclear pore complex. Depletion of individual importin-α proteins results in a failure of hTERT nuclear import, and the resulting cytoplasmic hTERT is degraded by ubiquitin-dependent proteolysis. Crystallographic analysis reveals that the bipartite NLS interacts with both the major and minor sites of importin-α proteins. We also show that Akt-mediated phosphorylation of S227 increases the binding affinity for importin-α proteins and promotes nuclear import of hTERT, thereby resulting in increased telomerase activity. These data provide details of a binding mechanism that enables hTERT to interact with the nuclear import receptors and of the control of the dynamic nuclear transport of hTERT through phosphorylation.

PubMed: 25999477
DOI: 10.1242/JCS.166132

Experimental method

X-RAY DIFFRACTION (2.52 Å)