Journal Article

FZJ-2024-06997

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Molecular basis of the CYFIP2 and NCKAP1 autism‐linked variants in the WAVE regulatory complex

Xie, S.FZJ* ; Zuo, K. (Corresponding author)FZJ* ; De Rubeis, S. ; Ruggerone, P. (Corresponding author) ; Carloni, P. (Corresponding author)FZJ*

2025
Protein Society Bethesda, Md.

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Please use a persistent id in citations: doi:10.1002/pro.5238  doi:10.34734/FZJ-2024-06997

Abstract: The WAVE regulatory pentameric complex regulates actin remodeling. Two components of it (CYFIP2 and NCKAP1) are encoded by genes whose genetic mutations increase the risk for Autism Spectrum Disorder (ASD) and related neurodevelopmental disorders. Here, we use a newly developed computational protocol and hotspot analysis to uncover the functional impact of these mutations at the interface of the correct isoforms of the two proteins into the complex. The mutations turn out to be located on the surfaces involving the largest number of hotspots of the complex. Most of them decrease the affinity of the proteins for the rest of the complex, but some have the opposite effect. The results are fully consistent with the available experimental data. The observed changes in the WAVE regulatory complex stability might impact on complex activation and ultimately play a role in the aberrant pathway of the complex, leading to the cell derangement associated with the disease.

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Contributing Institute(s):

1. Computational Biomedicine (INM-9)

Research Program(s):

1. 5252 - Brain Dysfunction and Plasticity (POF4-525) (POF4-525)

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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