2021
DOI: 10.1042/bcj20200799
|View full text |Cite
|
Sign up to set email alerts
|

Weakening of interaction networks with aging in tip-link protein induces hearing loss

Abstract: Age-related hearing loss (ARHL) is a common condition in humans marking the gradual decrease in hearing with age. Perturbations in the tip-link protein cadherin-23 that absorbs the mechanical tension from sound and maintains the integrity of hearing is associated with ARHL. Here, in search of molecular origins for ARHL, we dissect the conformational behavior of cadherin-23 along with the mutant S47P that progresses the hearing loss drastically. Using an array of experimental and computational approaches, we hi… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

1
17
0

Year Published

2021
2021
2024
2024

Publication Types

Select...
4
2

Relationship

3
3

Authors

Journals

citations
Cited by 7 publications
(18 citation statements)
references
References 72 publications
1
17
0
Order By: Relevance
“…6). Reportedly, the chemical and the thermal stabilities also followed the decreasing order from V47 to P47 variant 30 . Accordingly, we measured the weakest force-resistance for Cdh23 P47 featuring force-induced extensions between 5 pN -15 pN, followed by Cdh23 S47 between 13 pN − 25 pN, and strongest for Cdh23 V47 between 19 pN − 38 pN (Fig.…”
Section: Resultsmentioning
confidence: 83%
See 2 more Smart Citations
“…6). Reportedly, the chemical and the thermal stabilities also followed the decreasing order from V47 to P47 variant 30 . Accordingly, we measured the weakest force-resistance for Cdh23 P47 featuring force-induced extensions between 5 pN -15 pN, followed by Cdh23 S47 between 13 pN − 25 pN, and strongest for Cdh23 V47 between 19 pN − 38 pN (Fig.…”
Section: Resultsmentioning
confidence: 83%
“…Cdh23 EC1 consists of nine β-strands interconnected by reverse β turns, 3 10 α-helix, and random coils (Fig. 1C) 29,30 . We used three variants, Cdh23 EC1 (S47), Cdh23 EC1(V47), and Cdh23 EC1(P47), with different native packing densities, long-range H-bond networks, and different crosscorrelated crankshaft types motions among β-strands 30 (Fig.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…Four distributions of Δ L C indicate the multistep unfolding of Cdh23 in both HAP and PAP. It may be noted that the multistep unfolding is already reported from an in silico pulling of a single domain of Cdh23 (Cdh23 EC1) 54 . Further, while analyzing individual force-extension curves, we notice differences in the unfolding patterns in the spectra for both HAP and PAP (Fig.…”
Section: Resultsmentioning
confidence: 85%
“…Nevertheless, as shown above, the WSME model has the potential to predict the effects of amino-acid substitutions on protein stability and folding by calculating the free-energy landscapes of wild-type and mutant proteins. Such calculations have provided useful insights for protein engineering and medical applications [ 22 , 44 , 64 , 84 , 85 , 86 ]. Naganathan et al proposed a framework for calculating the stability of mutants using the WSME model and developed two programs, pStab [ 21 ] and pPerturb [ 22 ], which are available online.…”
Section: Prediction Of Folding Mechanismsmentioning
confidence: 99%