Structure–function relationships in protein homorepeats

Elena-Real, Carlos A.; Mier, Pablo; Sibille, Nathalie; Andrade-Navarro, Miguel A.; Bernadó, Pau

doi:10.1016/j.sbi.2023.102726

Cited by 5 publications

(1 citation statement)

References 102 publications

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“…The phenotypic diversity of homorepeat sequences is linked to tract length variations. Also, the polymorphic traits are observed among populations of the same organisms, and within different cell types, revealing the homorepeats’ instability and high propensities for cytotoxic behavior [ 4 , 5 , 6 ]. However, the exact origin of these genetically harmful and unstable tendencies remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Reviewing the Structure–Function Paradigm in Polyglutamine Disorders: A Synergistic Perspective on Theoretical and Experimental Approaches

Moldovean-Cioroianu

2024

IJMS

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Polyglutamine (polyQ) disorders are a group of neurodegenerative diseases characterized by the excessive expansion of CAG (cytosine, adenine, guanine) repeats within host proteins. The quest to unravel the complex diseases mechanism has led researchers to adopt both theoretical and experimental methods, each offering unique insights into the underlying pathogenesis. This review emphasizes the significance of combining multiple approaches in the study of polyQ disorders, focusing on the structure–function correlations and the relevance of polyQ-related protein dynamics in neurodegeneration. By integrating computational/theoretical predictions with experimental observations, one can establish robust structure–function correlations, aiding in the identification of key molecular targets for therapeutic interventions. PolyQ proteins’ dynamics, influenced by their length and interactions with other molecular partners, play a pivotal role in the polyQ-related pathogenic cascade. Moreover, conformational dynamics of polyQ proteins can trigger aggregation, leading to toxic assembles that hinder proper cellular homeostasis. Understanding these intricacies offers new avenues for therapeutic strategies by fine-tuning polyQ kinetics, in order to prevent and control disease progression. Last but not least, this review highlights the importance of integrating multidisciplinary efforts to advancing research in this field, bringing us closer to the ultimate goal of finding effective treatments against polyQ disorders.

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Section: Introductionmentioning

confidence: 99%