Lysosomal integral membrane protein-2 as a phospholipid receptor revealed by biophysical and cellular studies

Conrad KS, Cheng T-W, Ysselstein D, Heybrock S, Hoth LR, Chrunyk BA, am Ende CW, Krainc D, Schwake M, Saftig P, Liu S, et al. (2017)
Nature Communications 8(1): 1908.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Conrad, Karen S.; Cheng, Ting-Wen; Ysselstein, Daniel; Heybrock, Saskia; Hoth, Lise R.; Chrunyk, Boris A.; am Ende, Christopher W.; Krainc, Dimitri; Schwake, MichaelUniBi ; Saftig, Paul; Liu, Shenping; Qiu, Xiayang
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Abstract / Bemerkung
Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) contributes to endosomal and lysosomal function. LIMP-2 deficiency is associated with neurological abnormalities and kidney failure and, as an acid glucocerebrosidase receptor, impacts Gaucher and Parkinson’s diseases. Here we report a crystal structure of a LIMP-2 luminal domain dimer with bound cholesterol and phosphatidylcholine. Binding of these lipids alters LIMP-2 from functioning as a glucocerebrosidase-binding monomer toward a dimeric state that preferentially binds anionic phosphatidylserine over neutral phosphatidylcholine. In cellular uptake experiments, LIMP-2 facilitates transport of phospholipids into murine fibroblasts, with a strong substrate preference for phosphatidylserine. Taken together, these biophysical and cellular studies define the structural basis and functional importance of a form of LIMP-2 for lipid trafficking. We propose a model whereby switching between monomeric and dimeric forms allows LIMP-2 to engage distinct binding partners, a mechanism that may be shared by SR-BI and CD36, scavenger receptor proteins highly homologous to LIMP-2.
Erscheinungsjahr
2017
Zeitschriftentitel
Nature Communications
Band
8
Ausgabe
1
Art.-Nr.
1908
eISSN
2041-1723
Page URI
https://pub.uni-bielefeld.de/record/2953333

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Conrad KS, Cheng T-W, Ysselstein D, et al. Lysosomal integral membrane protein-2 as a phospholipid receptor revealed by biophysical and cellular studies. Nature Communications. 2017;8(1): 1908.
Conrad, K. S., Cheng, T. - W., Ysselstein, D., Heybrock, S., Hoth, L. R., Chrunyk, B. A., am Ende, C. W., et al. (2017). Lysosomal integral membrane protein-2 as a phospholipid receptor revealed by biophysical and cellular studies. Nature Communications, 8(1), 1908. https://doi.org/10.1038/s41467-017-02044-8
Conrad, K. S., Cheng, T. - W., Ysselstein, D., Heybrock, S., Hoth, L. R., Chrunyk, B. A., am Ende, C. W., Krainc, D., Schwake, M., Saftig, P., et al. (2017). Lysosomal integral membrane protein-2 as a phospholipid receptor revealed by biophysical and cellular studies. Nature Communications 8:1908.
Conrad, K.S., et al., 2017. Lysosomal integral membrane protein-2 as a phospholipid receptor revealed by biophysical and cellular studies. Nature Communications, 8(1): 1908.
K.S. Conrad, et al., “Lysosomal integral membrane protein-2 as a phospholipid receptor revealed by biophysical and cellular studies”, Nature Communications, vol. 8, 2017, : 1908.
Conrad, K.S., Cheng, T.-W., Ysselstein, D., Heybrock, S., Hoth, L.R., Chrunyk, B.A., am Ende, C.W., Krainc, D., Schwake, M., Saftig, P., Liu, S., Qiu, X., Ehlers, M.D.: Lysosomal integral membrane protein-2 as a phospholipid receptor revealed by biophysical and cellular studies. Nature Communications. 8, : 1908 (2017).
Conrad, Karen S., Cheng, Ting-Wen, Ysselstein, Daniel, Heybrock, Saskia, Hoth, Lise R., Chrunyk, Boris A., am Ende, Christopher W., Krainc, Dimitri, Schwake, Michael, Saftig, Paul, Liu, Shenping, Qiu, Xiayang, and Ehlers, Michael D. “Lysosomal integral membrane protein-2 as a phospholipid receptor revealed by biophysical and cellular studies”. Nature Communications 8.1 (2017): 1908.
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