Information à propos de mutations liés aux MG canal lent

Rubrique ouverte à tous en lecture seule.
POUR ACCEDER AUX NOMBREUX AUTRES FORUMS IL EST NECESSAIRE DE S'INSCRIRE (fonction M'enregistrer en haut à droite de l'écran).
Répondre
Avatar du membre

Auteur du sujet
Pboulanger
Administrateur
Administrateur
Messages : 4717
Enregistré le : 02 févr. 2010 18:41
Localisation : La Chapelle en Serval F-60520
    Windows 8.1 Firefox
Genre :
Zodiaque : Lion
Âge : 61
Contact :
France

Information à propos de mutations liés aux MG canal lent

Message par Pboulanger » 05 juil. 2016 19:24

:hi:

Lu sur http://onlinelibrary.wiley.com/doi/10.1 ... 23043/full
Traduction disponible directement en cliquant en bas à droite de ce message sur notre forum
Image
Mutations Causing Slow-Channel Myasthenia Reveal that a Valine ring in the Channel Pore of Muscle AChR is Optimized for Stabilizing Channel Gating
Authors
Shen, X.-M., Okuno, T., Milone, M., Otsuka, K., Takahashi, K., Komaki, H., Giles, E., Ohno, K. and Engel, A. G. (2016),
Accepted manuscript online: 4 July 2016Full publication history
DOI: 10.1002/humu.23043View/save citation


We identify two novel mutations in acetylcholine receptor (AChR) causing a slow-channel congenital myasthenia syndrome (CMS) in three unrelated patients (Pts).

Pt 1 harbors a heterozygous βV266A mutation (p.Val289Ala) in the second transmembrane domain (M2) of the AChR β subunit (CHRNB1).

Pts 2 and 3 carry the same mutation at an equivalent site in the ε subunit (CHRNE), εV265A (p.Val285Ala).

The mutant residues are conserved across all AChR subunits of all species and are components of a valine ring in the channel pore which is positioned four residues above the leucine ring.

Both βV266A and εV265A reduce the amino acid size and lengthen the channel opening bursts by 4.0-fold by enhancing gating efficiency by approximately 30-fold.

Substitution of alanine for valine at the corresponding position in the δ and α subunit prolongs the burst duration 4- and 8-fold, respectively.

Replacing valine at ε codon 265 either by a still smaller glycine or by a larger leucine also lengthens the burst duration.

Our analysis reveals that each valine in the valine ring contributes to channel kinetics equally, and the valine ring has been optimized in the course of evolution to govern channel gating.
Amicalement,
Image

Répondre

Retourner vers « Informations »