NeuralCipher Research overview
The text below is the source article’s original abstract under a verified reuse license. cc by
Background and Objectives: Intrinsically disordered proteins (IDPs) and proteins containing intrinsically disordered regions (IDRs) are known to be involved in various human diseases. Since the IDPs/IDRs are fluctuating between many structural substrates, the dynamical behavior of the disease-related IDPs/IDRs needs to be characterized to elucidate the mechanisms of the pathogenesis of the diseases. As protein motions have a hierarchy ranging from local side-chain motions, through segmental motions of loops or disordered regions, to diffusive motions of entire molecules, segmental motions, as well as local motions, need to be characterized. Materials and Methods: Combined analysis of quasielastic neutron scattering (QENS) spectra with the structural data provides information on both the segmental motions and the local motions of the IDPs/IDRs. Here, this method is applied to re-analyze the QENS spectra of the troponin core domain (Tn-CD), various mutants of which cause the pathogenesis of familial cardiomyopathy (FCM), and α-synuclein (αSyn), amyloid fibril formation of which is closely related to the pathogenesis of Parkinson's disease, collected in the previous studies. The dynamical behavior of wild-type Tn-CD, FCM-related mutant Tn-CD, and αSyn in the different propensity states for fibril formation is characterized. Results: In the Tn-CD, the behavior of the segmental motions is shown to be different between the wild type and the mutant. This difference is likely to arise from changes in the intramolecular interactions, which are suggested to be related to the functional aberration of the mutant Tn-CD. In αSyn, concerted enhancement of the segmental motions and the local motions is observed with an increased propensity for fibril formation, suggesting the importance of these motions in fibril formation. Conclusions: Characterization of the segmental motions as well as the local motions is thus useful for discussing how the changes in dynamical behavior caused by the disease-related mutations and/or environmental changes could be related to the functional and/or behavioral aberrations of these proteins.
Scientific assessment
Research question
Assess the question within the original study’s scope.
Methods & sample
Check the source article for study design and sample details.
Key findings
An editorially approved findings summary is not yet published for this record.
Limitations
Generalizability, bias and clinical meaning require separate assessment.
Methods, samples and clinical conclusions are not inferred from bibliographic metadata.