Structured Tandem Repeats in Protein Interactions.

Tandem repeats (TRs) in protein sequences are consecutive, highly similar sequence motifs. Some types of TRs fold into structural units that pack together in ensembles, forming either an (open) elongated domain or a (closed) propeller, where the last unit of the ensemble packs against the first one. Here, we examine TR proteins (TRPs) to see how their sequence, structure, and evolutionary properties favor them for a function as mediators of protein interactions.

Intranuclear inclusions of polyQ-expanded ATXN1 sequester RNA molecules.

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disease caused by a trinucleotide (CAG) repeat expansion in the ATXN1 gene. It is characterized by the presence of polyglutamine (polyQ) intranuclear inclusion bodies (IIBs) within affected neurons. In order to investigate the impact of polyQ IIBs in SCA1 pathogenesis, we generated a novel protein aggregation model by inducible overexpression of the mutant ATXN1(Q82) isoform in human neuroblastoma SH-SY5Y cells.

Selection of Multi-Drug Targets against Drug-Resistant XDR1219 Using the Hyperbolic Mapping of the Protein Interaction Network.

Tuberculosis remains the leading cause of death from a single pathogen. On the other hand, antimicrobial resistance (AMR) makes it increasingly difficult to deal with this disease. We present the hyperbolic embedding of the protein interaction network (mtbPIN) of resistant strain (MTB XDR1219) to determine the biological relevance of its latent geometry.

Analysis of Huntington's Disease Modifiers Using the Hyperbolic Mapping of the Protein Interaction Network.

Huntington's disease (HD) is caused by the production of a mutant huntingtin (HTT) with an abnormally long poly-glutamine (polyQ) tract, forming aggregates and inclusions in neurons. Previous work by us and others has shown that an increase or decrease in polyQ-triggered aggregates can be passive simply due to the interaction of proteins with the aggregates. To search for proteins with active (functional) effects, which might be more effective in finding therapies and mechanisms of HD, we selected among the proteins that interact with HTT a total of 49 pairs of proteins that, while being paralogous to each other (and thus expected to have similar passive interaction with HTT), are located in different regions of the protein interaction network (suggesting participation in different pathways or complexes).

Dynamics of a Protein Interaction Network Associated to the Aggregation of polyQ-Expanded Ataxin-1.

Background: Several experimental models of polyglutamine (polyQ) diseases have been previously developed that are useful for studying disease progression in the primarily affected central nervous system. However, there is a missing link between cellular and animal models that would indicate the molecular defects occurring in neurons and are responsible for the disease phenotype in vivo.

Methods: Here, we used a computational approach to identify dysregulated pathways shared by an in vitro and an in vivo model of ATXN1(Q82) protein aggregation, the mutant protein that causes the neurodegenerative polyQ disease spinocerebellar ataxia type-1 (SCA1).