1. Academic Validation
  2. Molecular basis for SNX-BAR-mediated assembly of distinct endosomal sorting tubules

Molecular basis for SNX-BAR-mediated assembly of distinct endosomal sorting tubules

  • EMBO J. 2012 Nov 28;31(23):4466-80. doi: 10.1038/emboj.2012.283.
Jan R T van Weering 1 Richard B Sessions Colin J Traer Daniel P Kloer Vikram K Bhatia Dimitrios Stamou Sven R Carlsson James H Hurley Peter J Cullen
Affiliations

Affiliation

  • 1 The Henry Wellcome Integrated Signalling Laboratories, School of Biochemistry, University of Bristol, Bristol, UK.
Abstract

Sorting nexins (SNXs) are regulators of endosomal sorting. For the SNX-BAR subgroup, a Bin/Amphiphysin/Rvs (BAR) domain is vital for formation/stabilization of tubular subdomains that mediate cargo recycling. Here, by analysing the in vitro membrane remodelling properties of all 12 human SNX-BARs, we report that some, but not all, can elicit the formation of tubules with diameters that resemble sorting tubules observed in cells. We reveal that SNX-BARs display a restricted pattern of BAR domain-mediated dimerization, and by resolving a 2.8 Å structure of a SNX1-BAR domain homodimer, establish that dimerization is achieved in part through neutralization of charged residues in the hydrophobic BAR-dimerization interface. Membrane remodelling also requires functional amphipathic helices, predicted to be present in all SNX-BARs, and the formation of high order SNX-BAR oligomers through selective 'tip-loop' interactions. Overall, the restricted and selective nature of these interactions provide a molecular explanation for how distinct SNX-BAR-decorated tubules are nucleated from the same endosomal vacuole, as observed in living cells. Our data provide insight into the molecular mechanism that generates and organizes the tubular endosomal network.

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