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Molecular basis for...
Molecular basis for SNX-BAR-mediated assembly of distinct endosomal sorting tubules
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van Weering, Jan R. T. (författare)
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Sessions, Richard B. (författare)
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Traer, Colin J. (författare)
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Kloer, Daniel P. (författare)
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Bhatia, Vikram K. (författare)
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Stamou, Dimitrios (författare)
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- Carlsson, Sven R. (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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Hurley, James H. (författare)
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Cullen, Peter J. (författare)
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(creator_code:org_t)
- 2012-10-19
- 2012
- Engelska.
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Ingår i: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 31:23, s. 4466-4480
- Relaterad länk:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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 angstrom 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- BAR domain
- phosphoinositide
- retromer
- sorting nexin
- VPS35
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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