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Structured and Intrinsically Disordered Domains within Amphiphysin1 Work Together to Sense and Drive Membrane Curvature


Cellular membranes undergo remodeling during many cellular processes including endocytosis, cytoskeletal protrusion, and organelle biogenesis. During these events, specialized proteins sense and amplify fluctuations in membrane curvature to create stably curved architectures. Amphiphysin1 is a multi-domain protein containing an N-terminal crescent-shaped BAR (Bin/Amphiphysin/Rvs) domain and a C-terminal domain that is largely disordered. When studied in isolation, the BAR domain of Amphiphysin1 senses membrane curvature and generates membrane tubules. However, the disordered domain has been largely overlooked in these studies. Interestingly, our recent work has demonstrated that the disordered domain is capable of substantially amplifying the membrane remodeling ability of the BAR domain. However, the physical mechanisms responsible for these effects are presently unclear. Here we elucidated the functional role of the disordered domain by gradually truncating it, creating a family of mutant proteins, which each contained the BAR domain and a fraction of the disordered domain. Using quantitative fluorescence and electron microscopy, our results indicate that the disordered domain contributes to membrane remodeling by making it more difficult for the protein to bind to and assemble on flat membrane surfaces. Specifically, we found that the disordered domain began to significantly impact membrane remodeling when its projected area exceeded that of the BAR domain. Once this threshold was crossed, steric interactions with the membrane surface and with neighboring disordered domains gave rise to increased curvature sensing and membrane vesiculation, respectively. These findings provide insight into the synergy between structured and disordered domains, which each play important biophysical roles in membrane remodeling.

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Publication details

The article was received on 23 Jul 2019, accepted on 10 Oct 2019 and first published on 11 Oct 2019

Article type: Paper
DOI: 10.1039/C9SM01495K
Soft Matter, 2019, Accepted Manuscript

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    Structured and Intrinsically Disordered Domains within Amphiphysin1 Work Together to Sense and Drive Membrane Curvature

    W. Zeno, W. T. Snead, A. S. Thatte and J. Stachowiak, Soft Matter, 2019, Accepted Manuscript , DOI: 10.1039/C9SM01495K

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