@article{HoeferDiLellaDahmanietal.2019,
  author    = {H{\"o}fer, C. T. and Di Lella, S. and Dahmani, Ismail and Jungnick, N. and Bordag, N. and Bobone, Sara and Huang, Q. and Keller, S. and Herrmann, A. and Chiantia, Salvatore},
  title     = {Structural determinants of the interaction between influenza A virus matrix protein M1 and lipid membranes},
  series = {Biochimica et biophysica acta : Biomembranes},
  volume    = {1861},
  journal   = {Biochimica et biophysica acta : Biomembranes},
  number    = {6},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0005-2736},
  doi       = {10.1016/j.bbamem.2019.03.013},
  pages     = {1123 -- 1134},
  year      = {2019},
  abstract  = {Influenza A virus is a pathogen responsible for severe seasonal epidemics threatening human and animal populations every year. One of the ten major proteins encoded by the viral genome, the matrix protein M1, is abundantly produced in infected cells and plays a structural role in determining the morphology of the virus. During assembly of new viral particles, M1 is recruited to the host cell membrane where it associates with lipids and other viral proteins. The structure of M1 is only partially known. In particular, structural details of M1 interactions with the cellular plasma membrane as well as M1 protein interactions and multimerization have not been clarified, yet. In this work, we employed a set of complementary experimental and theoretical tools to tackle these issues. Using raster image correlation, surface plasmon resonance and circular dichroism spectroscopies, we quantified membrane association and oligomerization of full-length M1 and of different genetically engineered M1 constructs (i.e., N- and C-terminally truncated constructs and a mutant of the polybasic region, residues 95-105). Furthermore, we report novel information on structural changes in M1 occurring upon binding to membranes. Our experimental results are corroborated by an all-atom model of the full-length M1 protein bound to a negatively charged lipid bilayer.},
  language  = {en}
}
@phdthesis{Dahmani2021,
  author    = {Dahmani, Ismail},
  title     = {Influenza A virus matrix protein M1},
  doi       = {10.25932/publishup-52740},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-527409},
  school      = {Universit{\"a}t Potsdam},
  pages     = {XI, 147},
  year      = {2021},
  abstract  = {Influenza A virus (IAV) is a pathogen responsible for severe seasonal epidemics threatening human and animal populations every year. During the viral assembly process in the infected cells, the plasma membrane (PM) has to bend in localized regions into a vesicle towards the extracellular side. Studies in cellular models have proposed that different viral proteins might be responsible for inducing membrane curvature in this context (including M1), but a clear consensus has not been reached. M1 is the most abundant protein in IAV particles. It plays an important role in virus assembly and budding at the PM. M1 is recruited to the host cell membrane where it associates with lipids and other viral proteins. However, the details of M1 interactions with the cellular PM, as well as M1-mediated membrane bending at the budozone, have not been clarified. In this work, we used several experimental approaches to analyze M1-lipids and M1-M1 interactions. By performing SPR analysis, we quantified membrane association for full-length M1 and different genetically engineered M1 constructs (i.e., N- and C-terminally truncated constructs and a mutant of the polybasic region). This allowed us to obtain novel information on the protein regions mediating M1 binding to membranes. By using fluorescence microscopy, cryogenic transmission electron microscopy (cryo-TEM), and three-dimensional (3D) tomography (cryo-ET), we showed that M1 is indeed able to cause membrane deformation on vesicles containing negatively-charged lipids, in the absence of other viral components. Further, sFCS analysis proved that simple protein binding is not sufficient to induce membrane restructuring. Rather, it appears that stable M1-M1 interactions and multimer formation are required to alter the bilayer three-dimensional structure through the formation of a protein scaffold. Finally, to mimic the budding mechanism in cells that arise by the lateral organization of the virus membrane components on lipid raft domains, we created vesicles with lipid domains. Our results showed that local binding of M1 to spatial confined acidic lipids within membrane domains of vesicles led to local M1 inward curvature.},
  language  = {en}
}