TY - JOUR T1 - Distribution of disease-causing germline mutations in coiled-coils suggests essential role of their N-terminal region JF - bioRxiv DO - 10.1101/2020.04.07.029165 SP - 2020.04.07.029165 AU - Zsofia E. Kalman AU - Bálint Mészáros AU - Zoltán Gáspári AU - Laszlo Dobson Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/04/08/2020.04.07.029165.abstract N2 - Next-generation sequencing resulted in the identification of a huge number of naturally occurring variations in human proteins. The correct interpretation of the functional effects of these variations necessitates the understanding of how they modulate protein structure. Coiled-coils are α-helical structures responsible for a diverse range of functions, but most importantly, they facilitate the structural organization of macromolecular scaffolds via oligomerization. In this study, we analyzed a comprehensive set of disease-associated germline mutations in coiled-coil structures. Our results highlight the essential role of residues near the N-terminal part of coiled-coil regions, possibly critical for superhelix assembly and folding in some cases. We also show that coiled-coils of different oligomerization states exhibit characteristically distinct patterns of disease-causing mutations. Our study provides structural and functional explanations on how disease emerges through the mutation of these structural motifs.Competing Interest StatementThe authors have declared no competing interest. ER -