Dynamic Interchange of Local Residue-Residue Interactions in the Largely Extended Single Alpha-Helix in Drebrin

Varga Soma; Péterfia Bálint Ferenc; Dudola Dániel; Farkas Viktor; Jeffries Cy M.; Permi Perttu; Gáspári Zoltán: Dynamic Interchange of Local Residue-Residue Interactions in the Largely Extended Single Alpha-Helix in Drebrin.
BIOCHEMICAL JOURNAL, 482 (8). pp. 383-399. ISSN 0264-6021 (2025)

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Folyóiratcikk

Szerző azonosítók:

Név	ORCID	MTMT szerző azonosító
Varga Soma		10079631
Péterfia Bálint Ferenc
Dudola Dániel
Farkas Viktor	0000-0002-8815-2783	10003129
Jeffries Cy M.
Permi Perttu
Gáspári Zoltán	0000-0002-8692-740X	10001271

Absztrakt (kivonat):

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.

Folyóirat címe:

BIOCHEMICAL JOURNAL

Megjelenés éve:

2025

Kötet:

482

Szám:

Oldalak:

pp. 383-399

ISSN:

0264-6021

Intézmény: