Journal Article

PUBDB-2025-01415

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dynamic Interchange of Local Residue-Residue Interactions in the Largely Extended Single Alpha-Helix in Drebrin

Varga, S. ; Péterfia, B. F. ; Dudola, D. ; Farkas, V. ; Jeffries, C. M. ; Permi, P. ; Gáspári, Z. (Corresponding author)

2025
Portland Press London

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Please use a persistent id in citations: doi:10.1042/BCJ20253036  doi:10.3204/PUBDB-2025-01415

Abstract: Single alpha-helices (SAHs) are protein regions with unique mechanical properties, forming long stable monomeric helical structures in solution. To date, only a few naturally occurring SAH regions have been extensively characterized, primarily from myosins, leaving the structural and dynamic variability of SAH regions largely unexplored. Drebrin (developmentally regulated brain protein) contains a predicted SAH segment with unique sequence characteristics, including aromatic residues within the SAH region and a preference for arginine over lysine in its C-terminal half. Using and NMR spectroscopy, combined with SAXS measurements, we demonstrate that the Drebrin-SAH is helical and monomeric in solution. NMR resonance assignment required specific 4D techniques to resolve severe signal overlap resulting from the low complexity and largely helical conformation of the sequence. To further characterize its structure, we generated a structural ensemble consistent with Cα, Cβ chemical shifts and SAXS data, revealing a primarily extended structure with non-uniform helicity. Our results suggest that dynamic rearrangement of salt bridges and potential transient cation-π interactions contribute to the formation and stabilization of both helical and non-helical local conformational states.

Note: ISSN 1470-8728 not unique: **2 hits**.

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Contributing Institute(s):

1. EMBL-User (EMBL-User)
2. EMBL (EMBL)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)

Experiment(s):

1. PETRA Beamline P12 (PETRA III)

Appears in the scientific report 2025

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