Analysis of the dominant mutation N188T of human connexin46 (hCx46) using concatenation and molecular dynamics simulation

Download statistics - Document (COUNTER):

Schadzek, Patrik; Stahl, Yannick; Preller, Matthias; Ngezahayo, Anaclet: Analysis of the dominant mutation N188T of human connexin46 (hCx46) using concatenation and molecular dynamics simulation. In: FEBS Open Bio 9 (2019), Nr. 8, S. 161-184. DOI:

Repository version

To cite the version in the repository, please use this identifier:

Selected time period:


Sum total of downloads: 42

Connexins (Cx) are proteins that form cell‐to‐cell gap junction channels. A mutation at position 188 in the second extracellular loop (E2) domain of hCx46 has been linked to an autosomal dominant zonular pulverulent cataract. As it is dominantly inherited, it is possible that the mutant variant affects the co‐expressed wild‐type Cx and/or its interaction with other cellular components. Here, we proposed to use concatenated hCx46wt‐hCx46N188T and hCx46N188T‐hCx46wt to analyze how hCx46N188T affected co‐expressed hCx46wt to achieve a dominant inheritance. Heterodimer hCx46wt‐hCx46N188T formed fewer gap junction plaques compared to homodimer hCx46wt‐hCx46wt, while the hCx46N188T‐hCx46N188T homodimer formed almost no gap junction plaques. Dye uptake experiments showed that hemichannels of concatenated variants were similar to hemichannels of monomers. Molecular dynamics simulations revealed that for docking, the N188 of a protomer was engaged in hydrogen bonds (HBs) with R180, N189, and D191 of the counterpart protomer of the adjacent hemichannel. T188 suppressed the formation of HBs between protomers. Molecular dynamics simulations of an equimolar hCx46wt/hCx46N188T gap junction channel revealed a reduced number of HBs between protomers, suggesting reduction of gap junction channels between lens fibers co‐expressing the variants.
License of this version: CC BY 4.0 Unported
Document Type: article
Publishing status: publishedVersion
Issue Date: 2019
Appears in Collections:Naturwissenschaftliche Fakultät

distribution of downloads over the selected time period:

downloads by country:

pos. country downloads
total perc.
1 image of flag of Germany Germany 37 88.10%
2 image of flag of United States United States 3 7.14%
3 image of flag of Cambodia Cambodia 2 4.76%

Further download figures and rankings:


Zur Erhebung der Downloadstatistiken kommen entsprechend dem „COUNTER Code of Practice for e-Resources“ international anerkannte Regeln und Normen zur Anwendung. COUNTER ist eine internationale Non-Profit-Organisation, in der Bibliotheksverbände, Datenbankanbieter und Verlage gemeinsam an Standards zur Erhebung, Speicherung und Verarbeitung von Nutzungsdaten elektronischer Ressourcen arbeiten, welche so Objektivität und Vergleichbarkeit gewährleisten sollen. Es werden hierbei ausschließlich Zugriffe auf die entsprechenden Volltexte ausgewertet, keine Aufrufe der Website an sich.

Search the repository