Modulation of Homer1 EVH1 domain internal dynamics by putative autism‐associated mutations

Farkas Fanni; Maruzs Brigitta; Kálmán Zsófia Etelka; Klumpler Tomas; Batta Gyula; Péterfia Bálint; Gáspári Zoltán: Modulation of Homer1 EVH1 domain internal dynamics by putative autism‐associated mutations.
FEBS LETTERS, 600 (16). pp. 2307-2319. ISSN 0014-5793 (2026)

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FEBSLetters-2026-Farkas-ModulationofHomer1EVH1domaininternaldynamicsbyputativeautismassociatedmutations.pdf - Megjelent verzió
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Folyóiratcikk

Szerző azonosítók:

Név	ORCID	MTMT szerző azonosító
Farkas Fanni		10076788
Maruzs Brigitta
Kálmán Zsófia Etelka		10065249
Klumpler Tomas
Batta Gyula	0000-0002-0442-1828	10007156
Péterfia Bálint		10026672
Gáspári Zoltán		10001271

Absztrakt (kivonat):

The EVH1 domain of the Homer1 scaffold protein interacts with the proline‐rich region of Shank3, forming a key network within the postsynaptic density. While two mutations (M65I and S97L) in the EVH1 domain have been suggested to be associated with autism spectrum disorder, our results show that neither mutation has a substantial effect on the overall structure or the partner binding properties of Homer1. Compared to the S97L variant, the M65I mutant exhibits larger chemical shift perturbations both upon the mutation itself and during partner binding, while also showing signs of thermal destabilization. Finally, integration of computational and NMR data suggests that both mutations perturb the μs‐ms timescale internal motions of the EVH1 domain.

Folyóirat címe:

FEBS LETTERS

Megjelenés éve:

2026

Kötet:

600

Szám:

Oldalak:

pp. 2307-2319

ISSN:

0014-5793

Intézmény: