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

Show simple item record

dc.identifier.uri http://dx.doi.org/10.15488/5336
dc.identifier.uri https://www.repo.uni-hannover.de/handle/123456789/5383
dc.contributor.author Schadzek, Patrik
dc.contributor.author Stahl, Yannick
dc.contributor.author Preller, Matthias
dc.contributor.author Ngezahayo, Anaclet
dc.date.accessioned 2019-09-03T11:52:13Z
dc.date.available 2019-09-03T11:52:13Z
dc.date.issued 2019
dc.identifier.citation 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: https://doi.org/10.1002/2211-5463.12624
dc.description.abstract 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. eng
dc.language.iso eng
dc.publisher Chichester : John Wiley and Sons Ltd
dc.relation.ispartofseries FEBS Open Bio 9 (2019), Nr. 8
dc.rights CC BY 4.0
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject Connexins (Cx) eng
dc.subject mutation N188T eng
dc.subject human connexin46 eng
dc.subject hCx46 eng
dc.subject.ddc 570 | Biowissenschaften, Biologie ger
dc.title Analysis of the dominant mutation N188T of human connexin46 (hCx46) using concatenation and molecular dynamics simulation
dc.type article
dc.type Text
dc.relation.issn 2211-5463
dc.relation.doi https://doi.org/10.1002/2211-5463.12624
dc.bibliographicCitation.issue 8
dc.bibliographicCitation.volume 9
dc.bibliographicCitation.firstPage 161
dc.bibliographicCitation.lastPage 184
dc.description.version publishedVersion
tib.accessRights frei zug�nglich


Files in this item

This item appears in the following Collection(s):

Show simple item record

 

Search the repository


Browse

My Account

Usage Statistics