4WO1

Crystal structure of the DAP12 transmembrane domain in lipid cubic phase

Summary for 4WO1

• Entry DOI: 10.2210/pdb4wo1/pdb
• Related: 2L34 2L35 4WOL
• Descriptor: TYRO protein tyrosine kinase-binding protein, CALCIUM ION, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, ... (4 entities in total)
• Functional Keywords: alpha-helix transmembrane signaling, signaling protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 15503.49

Authors

Call, M.J.,Call, M.E.,Knoblich, K. (deposition date: 2014-10-15, release date: 2015-06-03, Last modification date: 2023-09-27)

Primary citation

Knoblich, K.,Park, S.,Lutfi, M.,van 't Hag, L.,Conn, C.E.,Seabrook, S.A.,Newman, J.,Czabotar, P.E.,Im, W.,Call, M.E.,Call, M.J.
Transmembrane Complexes of DAP12 Crystallized in Lipid Membranes Provide Insights into Control of Oligomerization in Immunoreceptor Assembly.
Cell Rep, 11:1184-1192, 2015

PubMed Abstract: 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 polar surfaces that govern intramembrane assembly with client receptors. We demonstrate that, in addition to the well-studied dimeric form, these trimeric and tetrameric structures are made in cells, and their formation is competitive with receptor association in the ER. The polar transmembrane sequences therefore act as primary determinants of oligomerization specificity through interplay between charge shielding and sequestration of polar surfaces within helix interfaces.

PubMed: 25981043
DOI: 10.1016/j.celrep.2015.04.045

Experimental method

X-RAY DIFFRACTION (2.14 Å)