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Cell Syst. 2017 Nov 22;5(5):518-526.e3. doi: 10.1016/j.cels.2017.10.004. Epub 2017 Nov 1.

Dash-and-Recruit Mechanism Drives Membrane Curvature Recognition by the Small Bacterial Protein SpoVM.

Author information

1
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
2
Department of Biochemistry and Molecular Biology, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA.
3
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: kchuang@stanford.edu.
4
Department of Biochemistry and Molecular Biology, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA. Electronic address: ftian@psu.edu.
5
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: ramamurthiks@mail.nih.gov.

Abstract

In Bacillus subtilis, sporulation requires that the 26-amino acid protein SpoVM embeds specifically into the forespore membrane, a structure with convex curvature. How this nanometer-sized protein can detect curves on a micrometer scale is not well understood. Here, we report that SpoVM exploits a "dash-and-recruit" mechanism to preferentially accumulate on the forespore. Using time-resolved imaging and flow cytometry, we observe that SpoVM exhibits a faster adsorption rate onto membranes of higher convex curvature. This preferential adsorption is accurately modeled as a two-step process: first, an initial binding event occurs with a faster on rate, then cooperative recruitment of additional SpoVM molecules follows. We demonstrate that both this biochemical process and effective sporulation in vivo require an unstructured and flexible SpoVM N terminus. We propose that this two-pronged strategy of fast adsorption followed by recruitment of subsequent molecules is a general mechanism that allows small proteins to detect subtle curves with a radius 1,000-fold their size.

KEYWORDS:

ALPS; ArfGAP1; BAR domain; DivIVA; PtdIns3KC3; SpoIVA; amphipathic helix; autophagy; geometric cue; septins

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