|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|
|Date Published||2020 10 15|
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.
|Alternate Journal||Sci Rep|
|PubMed Central ID||PMC7562717|