Molecular basis for SNX-BAR-mediated assembly of distinct endosomal sorting tubules
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Molecular basis for SNX-BAR-mediated assembly of distinct endosomal sorting tubules. / van Weering, Jan R.T.; Sessions, Richard B.; Traer, Colin J.; Kloer, Daniel P.; Bhatia, Vikram K.; Stamou, Dimitrios; Carlsson, Sven R.; Hurley, James H.; Cullen, Peter J.
In: E M B O Journal, Vol. 31, No. 23, 2012, p. 4466-4480.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Molecular basis for SNX-BAR-mediated assembly of distinct endosomal sorting tubules
AU - van Weering, Jan R.T.
AU - Sessions, Richard B.
AU - Traer, Colin J.
AU - Kloer, Daniel P.
AU - Bhatia, Vikram K.
AU - Stamou, Dimitrios
AU - Carlsson, Sven R.
AU - Hurley, James H.
AU - Cullen, Peter J.
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
U2 - 10.1038/emboj.2012.283
DO - 10.1038/emboj.2012.283
M3 - Journal article
C2 - 23085988
VL - 31
SP - 4466
EP - 4480
JO - E M B O Journal
JF - E M B O Journal
SN - 0261-4189
IS - 23
ER -
ID: 45763665