Dynamical Behavior of Disordered Regions in Disease-Related Proteins Revealed by Quasielastic Neutron Scattering

Fujiwara, Satoru

doi:10.3390/medicina58060795

Cited by 1 publication

(2 citation statements)

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“…Recently, studies of IDRs and IDPs have become increasingly relevant due to their involvement in important cellular processes, including cell signaling, protein regulation, and transmembrane transport [ 9 ]. The disorder allows these proteins to change conformation, allowing flexibility [ 10 ]. Because of their importance in cellular interaction, IDPs are tightly regulated and, when altered, are implicated in various diseases [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Initial Investigations of Intrinsically Disordered Regions in Inherited Retinal Diseases

Lee

Procopio

Pulido

et al. 2023

IJMS

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Intrinsically disordered regions (IDRs) are protein regions that are unable to fold into stable tertiary structures, enabling their involvement in key signaling and regulatory functions via dynamic interactions with diverse binding partners. An understanding of IDRs and their association with biological function may help elucidate the pathogenesis of inherited retinal diseases (IRDs). The main focus of this work was to investigate the degree of disorder in 14 proteins implicated in IRDs and their relationship with the number of pathogenic missense variants. Metapredict, an accurate, high-performance predictor that reproduces consensus disorder scores, was used to probe the degree of disorder as a function of the amino acid sequence. Publicly available data on gnomAD and ClinVar was used to analyze the number of pathogenic missense variants. We show that proteins with an over-representation of missense variation exhibit a high degree of disorder, and proteins with a high amount of disorder tolerate a higher degree of missense variation. These proteins also exhibit a lower amount of pathogenic missense variants with respect to total missense variants. These data suggest that protein function may be related to the overall level of disorder and could be used to refine variant interpretation in IRDs.

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Section: Introductionmentioning

confidence: 99%

“…Because of their importance in cellular interaction, IDPs are tightly regulated and, when altered, are implicated in various diseases [ 9 ]. More specifically, IDPs have been analyzed in the context of cancer, cardiovascular, and neurodegenerative disease and are postulated as a target for therapeutic modalities [ 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%