@article{b4552e160d3f49bca8ad08409be6f00b,
title = "Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DcR3",
abstract = "The apoptotic effect of FasL:Fas signaling is disrupted by DcR3, a unique secreted member of the tumor necrosis factor receptor superfamily, which also binds and neutralizes TL1A and LIGHT. DcR3 is highly elevated in patients with various tumors and contributes to mechanisms by which tumor cells to evade host immune surveillance. Here we report the crystal structure of FasL in complex with DcR3. Comparison of FasL:DcR3 structure with our earlier TL1A:DcR3 and LIGHT:DcR3 structures supports a paradigm involving the recognition of invariant main-chain and conserved side-chain functionalities, which is responsible for the recognition of multiple TNF ligands exhibited by DcR3. The FasL:DcR3 structure also provides insight into the FasL:Fas recognition surface. We demonstrate that the ability of recombinant FasL to induce Jurkat cell apoptosis is significantly enhanced by native glycosylation or by structure-inspired mutations, both of which result in reduced tendency to aggregate. All of these activities are efficiently inhibited by recombinant DcR3.",
author = "Weifeng Liu and Udupi Ramagopal and Huiyong Cheng and Bonanno, {Jeffrey B.} and Rafael Toro and Rahul Bhosle and Chenyang Zhan and Almo, {Steven C.}",
note = "Funding Information: Data for this study were collected at beamline X29 of the National Synchrotron Light Source at Brookhaven National Laboratory and the Lilly Research Laboratories Collaborative Access Team (LRL-CAT) beamline at Sector 31 of the Advanced Photon Source. Financial support for X29 comes principally from the Offices of Biological and Environmental Research and of Basic Energy Sciences of the US Department of Energy , and from the National Center for Research Resources ( P41RR012408 ), the National Institute of General Medical Sciences ( P41GM103473 ) of the NIH , and the National Institute of Biomedical Imaging and Bioengineering (NIBIB) ( P30-EB-09998 ). We thank Dr. Wuxian Shi for the assistance at the X29 beamline site. This research used resources of the Advanced Photon Source, a US Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Use of the Lilly Research Laboratories Collaborative Access Team (LRL-CAT) beamline at Sector 31 of the Advanced Photon Source was provided by Eli Lilly Company, which operates the facility. We thank Mengyan Li for assisting with Jurkat cell culture. We acknowledge the contributions of Dr. Stanley G. Nathenson to the early stages of this project. This work was supported by the NIH Grants GM094662 and GM094665 (S.C.A.); we also acknowledge support from the Albert Einstein Cancer Center ( P30CA013330 ) and the Einstein Crystallographic Core X-ray Diffraction Facility supported by NIH Shared Instrumentation Grant S10 OD020068 . This work was partially supported by the Price Family Foundation and contributions to the Albert Einstein Center for Experimental Therapeutics by Pamela and Edward S. Pantzer. Publisher Copyright: {\textcopyright} 2016 Elsevier Ltd",
year = "2016",
month = nov,
day = "1",
doi = "10.1016/j.str.2016.09.009",
language = "English (US)",
volume = "24",
pages = "2016--2023",
journal = "Structure with Folding & design",
issn = "0969-2126",
publisher = "Cell Press",
number = "11",
}