Biology subjects

Joseph, A. P.

Publications and source records attributed to Joseph, A. P..

2 recordsLinked to original sources

bioRxiv2018

CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers

The membrane attack complex (MAC) is one of the immune systems first responders. Complement proteins assemble on target membranes to form pores that lyse pathogens and impact tissue homeostasis of self-cells. How MAC disrupts the membrane barrier remains unclear. Here we use electron cryo-microscopy and flicker spectroscopy to show that MAC interacts with lipid bilayers in two distinct ways. Whereas C6 and C7 associate with the outer leaflet and reduce the energy for membrane bending, C8 and C9 traverse the bilayer increasing membrane rigidity. CryoEM reconstructions reveal plasticity of the MAC pore and demonstrate how C5b6 acts as a platform, directing assembly of a giant {beta}-barrel whose structure is supported by a glycan scaffold. Our work provides a structural basis for understanding how {beta}-pore forming proteins breach the membrane and reveals a mechanism for how MAC kills pathogens and regulates cell functions.

biophysics↗

bioRxiv2017

PBxplore: A Tool To Analyze Local Protein Structure And Deformability With Protein Blocks

Proteins are highly dynamic macromolecules. A classical way to analyze their inner flexibility is to perform molecular dynamics simulations. In this context, we present the advantage to use small structural prototypes, namely the Protein Blocks (PBs). PBs give a good approximation of the local structure of the protein backbone. More importantly, by reducing the conformational complexity of protein structures, they allow analyzes of local protein deformability which cannot be done with other methods and had been used efficiently in different applications. PBxplore is a suite of tools to analyze the dynamics and deformability of protein structures using PBs. It is able to process large amount of data such as those produced by molecular dynamics simulations. It produces various outputs with text and graphics, such as frequencies, entropy and information logo. PBxplore is available at https://github.com/pierrepo/PBxplore and is released under the open-source MIT license.

bioinformatics↗