Journal article

Transmembrane Complexes of DAP12 Crystallized in Lipid Membranes Provide Insights into Control of Oligomerization in Immunoreceptor Assembly

Konstantin Knoblich, Soohyung Park, Mariam Lutfi, Leonie van 't Hag, Charlotte E Conn, Shane A Seabrook, Janet Newman, Peter E Czabotar, Wonpil Im, Matthew E Call, Melissa J Call

CELL REPORTS | CELL PRESS | Published : 2015


The membrane-spanning α helices of single-pass receptors play crucial roles in stabilizing oligomeric structures and transducing biochemical signals across the membrane. Probing intermolecular transmembrane interactions in single-pass receptors presents unique challenges, reflected in a gross underrepresentation of their membrane-embedded domains in structural databases. Here, we present two high-resolution structures of transmembrane assemblies from a eukaryotic single-pass protein crystallized in a lipidic membrane environment. Trimeric and tetrameric structures of the immunoreceptor signaling module DAP12, determined to 1.77-Å and 2.14-Å resolution, respectively, are organized by the same..

View full abstract


Awarded by National Health and Medical Research Council (NHMRC) of Australia

Awarded by Victorian Government

Awarded by XSEDE

Awarded by National Science Foundation

Awarded by National Institutes of Health

Awarded by QEII Fellowship from the Australian Research Council (ARC)

Awarded by ARC Future Fellowship


Awarded by Div Of Molecular and Cellular Bioscience

Funding Acknowledgements

We thank David Aragao for helpful advice on LCP crystallization, Pooja Sharma for solution NMR analysis of DAP12-TM peptides, Emilia Wu for assistance with MD simulations, Peter Colman and Jacqui Gulbis for assistance with data processing and refinement and for much helpful discussion, and members of M.E.C.'s and M.J.C.'s laboratory for reading the manuscript. This work was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia (GNT1011352 to M.J.C. and M.E.C., GNT1059331 to P.E.C.; Infrastructure Support [IRIISS] to WEHI), the Victorian Government (VESKI Innovation Fellowship VIF12 to M.E.C.; Operational Infrastructure Support to WEHI), XSEDE MCB070009 (to W.I.), the National Science Foundation (NSF MCB-1157677 to W.I.) and the National Institutes of Health (NIH R01-GM092950 to W.I.). M.E.C. is supported by a QEII Fellowship (DP110104369) from the Australian Research Council (ARC). M.J.C. is supported by an ARC Future Fellowship (FT120100145). Part of this research was carried out at the MX2 and SAXS/WAXS beamlines of the Australian Synchrotron, and we thank the beamline scientists for their technical support. We also acknowledge the use of the CSIRO Collaborative Crystallisation Centre.