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Roca-Martínez, J.* ; Kang, H.-S. ; Sattler, M. ; Vranken, W.F.*

Analysis of the inter-domain orientation of tandem RRM domains with diverse linkers: Connecting experimental with AlphaFold2 predicted models.

NAR Gen. Bioinfo. 6:lqae002 (2024)
Publ. Version/Full Text DOI PMC
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The RNA recognition motif (RRM) is the most prevalent RNA binding domain in eukaryotes and is involved in most RNA metabolism processes. Single RRM domains have a limited RNA specificity and affinity and tend to be accompanied by other RNA binding domains, frequently additional RRMs that contribute to an avidity effect. Within multi-RRM proteins, the most common arrangement are tandem RRMs, with two domains connected by a variable linker. Despite their prevalence, little is known about the features that lead to specific arrangements, and especially the role of the connecting linker. In this work, we present a novel and robust way to investigate the relative domain orientation in multi-domain proteins using inter-domain vectors referenced to a stable secondary structure element. We apply this method to tandem RRM domains and cluster experimental tandem RRM structures according to their inter-domain and linker-domain contacts, and report how this correlates with their orientation. By extending our analysis to AlphaFold2 predicted structures, with particular attention to the inter-domain predicted aligned error, we identify new orientations not reported experimentally. Our analysis provides novel insights across a range of tandem RRM orientations that may help for the design of proteins with a specific RNA binding mode.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 2631-9268
e-ISSN 2631-9268
Journal NAR: Genomics and Bioinformatics
Quellenangaben Volume: 6, Issue: 1, Pages: , Article Number: lqae002 Supplement: ,
Publisher Oxford University Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Structural Biology (STB)