Single-particle EM reveals extensive conformational variability of the Ltn1 E3 ligase Journal Article
| Authors: | Lyumkis, D.; Doamekpor, S. K.; Bengtson, M. H.; Lee, J. W.; Toro, T. B.; Petroski, M. D.; Lima, C. D.; Potter, C. S.; Carragher, B.; Joazeiro, C. A. P. |
| Article Title: | Single-particle EM reveals extensive conformational variability of the Ltn1 E3 ligase |
| Abstract: | Ltn1 is a 180-kDa E3 ubiquitin ligase that associates with ribosomes and marks certain aberrant, translationally arrested nascent polypeptide chains for proteasomal degradation. In addition to its evolutionarily conserved large size, Ltn1 is characterized by the presence of a conserved N terminus, HEAT/ARM repeats predicted to comprise the majority of the protein, and a C-terminal catalytic RING domain, although the protein's exact structure is unknown. We used numerous single-particle EM strategies to characterize Ltn1's structure based on negative stain and vitreous ice data. Two-dimensional classifications and subsequent 3D reconstructions of electron density maps show that Ltn1 has an elongated form and presents a continuum of conformational states about two flexible hinge regions, whereas its overall architecture is reminiscent of multisubunit cullin-RING ubiquitin ligase complexes. We propose a model of Ltn1 function based on its conformational variability and flexibility that describes how these features may play a role in cotranslational protein quality control. |
| Keywords: | unclassified drug; protein conformation; protein motif; protein analysis; protein structure; ubiquitin protein ligase e3; bioinformatics; conformational heterogeneity; alpha helix; ltn1/listerin; neurodegenerative disease; ring e3 ubiquitin ligase; translational surveillance; ltn1 ligase |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 110 |
| Issue: | 5 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2013-01-29 |
| Start Page: | 1702 |
| End Page: | 1707 |
| Language: | English |
| DOI: | 10.1073/pnas.1210041110 |
| PROVIDER: | scopus |
| PMCID: | PMC3562785 |
| PUBMED: | 23319619 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 March 2013" - "CODEN: PNASA" - "Source: Scopus" |
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