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Theses
Etude par modélisation moléculaire des propriétés mécaniques d'un système membranaire : le canal mécanosensible MscL au sein de bicouches lipidiques modèles
Etude par modélisation moléculaire des propriétés mécaniques d'un système membranaire : le canal mécanosensible MscL au sein de bicouches lipidiques modèles
Abstract : Mechanosensitive channels of Large conductance (MscL) are integral membrane proteins that permit the bacterium to survive when hypo-osmotic shock occurs. Their principal characteristic is to open in response to a mechanical stress : a tension of the membrane. The comprehension of their mode of activation is necessary to work out a global model of the mechanism of sensitivity to membrane tension.
We studied here the first stages of the gating mechanism of MscL induced by membrane thinning, as well as the interactions controlling these conformational changes by simulations of molecular dynamics. The comparison of the principal component analysis of the tra jectories and the directions given by the normal modes analysis enabled us to highlight the influence of the membrane on the intrinsic dynamics of the channel. We then studied MscL channels from various organisms and having different sensitivity. Significant differences between the behaviors of the two systems plunged in membranes of variable thickness were highlighted. These differences led us to explore the role of the various domains and in particular the role of the periplasmic loops by building hybrid channels by combination of domains from different organisms. The results obtained confirm the fundamental role of the periplasmic loops in the sensitivity of the MscL.
We studied here the first stages of the gating mechanism of MscL induced by membrane thinning, as well as the interactions controlling these conformational changes by simulations of molecular dynamics. The comparison of the principal component analysis of the tra jectories and the directions given by the normal modes analysis enabled us to highlight the influence of the membrane on the intrinsic dynamics of the channel. We then studied MscL channels from various organisms and having different sensitivity. Significant differences between the behaviors of the two systems plunged in membranes of variable thickness were highlighted. These differences led us to explore the role of the various domains and in particular the role of the periplasmic loops by building hybrid channels by combination of domains from different organisms. The results obtained confirm the fundamental role of the periplasmic loops in the sensitivity of the MscL.
Cited literature [206 references]
https://tel.archives-ouvertes.fr/tel-00189606
Contributor : Gaelle Debret Connect in order to contact the contributor
Submitted on : Wednesday, November 21, 2007 - 2:47:36 PM
Last modification on : Saturday, March 28, 2020 - 2:09:23 AM
Long-term archiving on: : Monday, September 24, 2012 - 3:51:00 PM
Contributor : Gaelle Debret Connect in order to contact the contributor
Submitted on : Wednesday, November 21, 2007 - 2:47:36 PM
Last modification on : Saturday, March 28, 2020 - 2:09:23 AM
Long-term archiving on: : Monday, September 24, 2012 - 3:51:00 PM