TY - JOUR

T1 - Glycosylation and Lipids Working in Concert Direct CD2 Ectodomain Orientation and Presentation

AU - Polley, Anirban

AU - Orłowski, Adam

AU - Danne, Reinis

AU - Gurtovenko, Andrey A.

AU - Bernardino de La Serna, Jorge

AU - Eggeling, Christian

AU - Davis, Simon J.

AU - Róg, Tomasz

AU - Vattulainen, Ilpo

N1 - Funding Information: We wish to thank the Academy of Finland (Center of Excellence in Biomembrane Research (T.R., I.V.)) and the European Research Council (Advanced Grant project CROWDED-PRO-LIPIDS) (I.V.) for financial support. We also thank the Medical Research Council (MRC, Grant Number MC_UU_12010/unit Programmes G0902418 and MC_UU_12025) and MRC/BBSRC/EPSRC (Grant Number MR/K01577X/1) for generous funding of J.B.d.l.S., S.D., and C.E., the Wellcome Trust for funding to S.D., and funding by the Marie Curie Career Integration Grant to J.B.d.l.S. For computational resources, we wish to thank the CSC - IT Center for Science (Espoo, Finland). Publisher Copyright: © 2017 American Chemical Society. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.

PY - 2017/3/2

Y1 - 2017/3/2

N2 - Proteins embedded in the plasma membrane mediate interactions with the cell environment and play decisive roles in many signaling events. For cell-cell recognition molecules, it is highly likely that their structures and behavior have been optimized in ways that overcome the limitations of membrane tethering. In particular, the ligand binding regions of these proteins likely need to be maximally exposed. Here we show by means of atomistic simulations of membrane-bound CD2, a small cell adhesion receptor expressed by human T-cells and natural killer cells, that the presentation of its ectodomain is highly dependent on membrane lipids and receptor glycosylation acting in apparent unison. Detailed analysis shows that the underlying mechanism is based on electrostatic interactions complemented by steric interactions between glycans in the protein and the membrane surface. The findings are significant for understanding the factors that render membrane receptors accessible for binding and signaling.

AB - Proteins embedded in the plasma membrane mediate interactions with the cell environment and play decisive roles in many signaling events. For cell-cell recognition molecules, it is highly likely that their structures and behavior have been optimized in ways that overcome the limitations of membrane tethering. In particular, the ligand binding regions of these proteins likely need to be maximally exposed. Here we show by means of atomistic simulations of membrane-bound CD2, a small cell adhesion receptor expressed by human T-cells and natural killer cells, that the presentation of its ectodomain is highly dependent on membrane lipids and receptor glycosylation acting in apparent unison. Detailed analysis shows that the underlying mechanism is based on electrostatic interactions complemented by steric interactions between glycans in the protein and the membrane surface. The findings are significant for understanding the factors that render membrane receptors accessible for binding and signaling.

UR - http://www.scopus.com/inward/record.url?scp=85014304459&partnerID=8YFLogxK

U2 - 10.1021/acs.jpclett.6b02824

DO - 10.1021/acs.jpclett.6b02824

M3 - Letter

C2 - 28191954

AN - SCOPUS:85014304459

VL - 8

SP - 1060

EP - 1066

JO - Journal of Physical Chemistry Letters

JF - Journal of Physical Chemistry Letters

SN - 1948-7185

IS - 5

ER -