Compound heterozygoty in patients with TTR-related amyloidosis

Alves, Irina; Jacobson, Daniel R.; Torres, MM; Coelho, Teresa; Holmgren, Gösta; Saraiva, M.J.M.

doi:10.1016/0960-8966(96)88824-9

Cited by 1 publication

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“…Yet, the higher atomic interactions could also provide more backup links contributing to the higher stability of T119M reported experimentally, and have thus no relation with the 50-58 segment allocation perturbations in L55P (McCutchen et al, 1995;Quintas et al, 2001;Dorantes-Gilardi et al, 2018). T119M is also known to prevent amyloidogenesis when present together with the V30M mutation in heterozygous individuals (Alves et al, 1996) and to protect the V30M TTR tetramer from dissociation in vitro when some V30M chains are replaced by T119M chains (Hammarstrom, 2001). This is another type of compensatory mechanism where the dynamics perturbation caused by the V30M mutation on one chain is corrected by a dynamics perturbation caused by the T119M mutation on another chain.…”

Section: Transthyretin Variantsmentioning

confidence: 99%

A computational methodology to diagnose sequence-variant dynamic perturbations by comparing atomic protein structures

Pacini

Lesieur

2021

Bioinformatics

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Motivation The objective is to diagnose dynamics perturbations caused by amino acid mutations as prerequisite to assess protein functional health or drug failure, simply using network models of protein X-ray structures. Results We find that the differences in the allocation of the atomic interactions of each amino acid to 1D, 2D, 3D, 4D structural levels between variants structurally robust, recover experimental dynamic perturbations. The allocation measure validated on two B-pentamers variants of AB5 toxins having 17 mutations, also distinguishes dynamic perturbations of pathogenic and non-pathogenic Transthyretin single-mutants. Finally, the main proteases of the coronaviruses SARS-CoV and SARS-CoV-2 exhibit changes in the allocation measure, raising the possibility of drug failure despite the main proteases structural similarity. Availability The Python code used for the production of the results is available at github.com/lorpac/protein_partitioning_atomic_contacts. The authors will run the analysis on any PDB structures of protein variants upon request. Supplementary information Supplementary data are available at Bioinformatics online.

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