RESUMO
Hepatitis D virus (HDV) is classified according to eight genotypes. The various genotypes are included in the HDVdb database, where each HDV sequence is specified by its genotype. In this contribution, a mathematical analysis is performed on RNA sequences in HDVdb. The RNA folding predicted structures of the Genbank HDV genome sequences in HDVdb are classified according to their coarse-grain tree-graph representation. The analysis allows discarding in a simple and efficient way the vast majority of the sequences that exhibit a rod-like structure, which is important for the virus replication, to attempt to discover other biological functions by structure consideration. After the filtering, there remain only a small number of sequences that can be checked for their additional stem-loops besides the main one that is known to be responsible for virus replication. It is found that a few sequences contain an additional stem-loop that is responsible for RNA editing or other possible functions. These few sequences are grouped into two main classes, one that is well-known experimentally belonging to genotype 3 for patients from South America associated with RNA editing, and the other that is not known at present belonging to genotype 7 for patients from Cameroon. The possibility that another function besides virus replication reminiscent of the editing mechanism in HDV genotype 3 exists in HDV genotype 7 has not been explored before and is predicted by eigenvalue analysis. Finally, when comparing native and shuffled sequences, it is shown that HDV sequences belonging to all genotypes are accentuated in their mutational robustness and thermodynamic stability as compared to other viruses that were subjected to such an analysis.
RESUMO
Proteins containing glutamine repeats (polyQ) are known to be structurally unstable. Abnormal expansion of polyQ in some proteins exceeding a certain threshold leads to neurodegenerative disease, a symptom of which are protein aggregates. This has led to extensive research of the structure of polyQ stretches. However, the accumulation of contradictory results suggests that protein context might be of importance. Here we aimed to evaluate the structural context of polyQ regions in proteins by analysing the secondary structure of polyQ proteins and their homologs. The results revealed that the secondary structure in polyQ vicinity is predominantly random coil or helix. Importantly, the regions surrounding the polyQ are often not solved in 3D structures. In the few cases where the point of insertion of the polyQ was mapped to a full protein, we observed that these are always located in the surface of the protein. The findings support the hypothesis that polyQ might serve to extend coiled coils at their C-terminus in highly disordered regions involved in protein-protein interactions.
