Title | Distribution of disease-causing germline mutations in coiled-coils implies an important role of their N-terminal region. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Kalman ZE, Mészáros B, Gáspári Z, Dobson L |
Journal | Sci Rep |
Volume | 10 |
Issue | 1 |
Pagination | 17333 |
Date Published | 2020 10 15 |
ISSN | 2045-2322 |
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 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 suggest an important 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. |
DOI | 10.1038/s41598-020-74354-9 |
Alternate Journal | Sci Rep |
PubMed ID | 33060664 |
PubMed Central ID | PMC7562717 |