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bioRxiv · 10.1101/2020.04.07.029165

Distribution of disease-causing germline mutations in coiled-coils suggests essential role of their N-terminal region

Kalman, Z. E.·Meszaros, B.·Gaspari, Z.·Dobson, L.
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Abstract

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 -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.

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Kalman, Z. E., Meszaros, B., Gaspari, Z., Dobson, L.. 2020-04-07. Distribution of disease-causing germline mutations in coiled-coils suggests essential role of their N-terminal region. https://doi.org/10.1101/2020.04.07.029165

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