Are different stoichiometries feasible for complexes between lymphotoxin-alpha and tumor necrosis factor receptor 1?

BMC Structural Biology
Nahren Manuel Mascarenhas, Johannes Kästner

Abstract

Tumor necrosis factors, TNF and lymphotoxin-α (LT), are cytokines that bind to two receptors, TNFR1 and TNFR2 (TNF-receptor 1 and 2) to trigger their signaling cascades. The exact mechanism of ligand-induced receptor activation is still unclear. It is generally assumed that three receptors bind to the homotrimeric ligand to trigger a signaling event. Recent evidence, though, has raised doubts if the ligand:receptor stoichiometry should indeed be 3:3 for ligand-induced cellular response. We used molecular dynamics simulations, elastic network models, as well as MM/PBSA to analyze this question. Applying MM/PBSA methodology to different stoichiometric complexes of human LT-(TNFR1)n=1,2,3 the free energy of binding in these complexes has been estimated by single-trajectory and separate-trajectory methods. Simulation studies rationalized the favorable binding energy in the LT-(TNFR1)1 complex, as evaluated from single-trajectory analysis to be an outcome of the interaction of cysteine-rich domain 4 (CRD4) and the ligand. Elastic network models (ENMs) help to associate the difference in the global fluctuation of the receptors in these complexes. Functionally relevant transformation associated with these complexes reveal the differen...Continue Reading

References

Sep 1, 1991·Somatic Cell and Molecular Genetics·A MilatovichU Francke
Oct 25, 1991·Proceedings of the National Academy of Sciences of the United States of America·L A TartagliaD V Goeddel
Jun 2, 1995·The Journal of Biological Chemistry·J H NaismithS R Sprang
Sep 10, 1993·Cell·L A TartagliaD V Goeddel
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Dec 1, 1995·Proteins·D Frishman, P Argos
Apr 16, 1998·Trends in Biochemical Sciences·J H Naismith, S R Sprang
Jun 15, 1999·Toxicologic Pathology·A BendeleM Guy
Jul 13, 2000·Microscopy Research and Technique·H T Idriss, J H Naismith
Feb 13, 2001·Biophysical Journal·A R AtilganI Bahar
Apr 5, 2001·Protein Engineering·F Tama, Y H Sanejouand
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·N A BakerJ A McCammon
Jul 4, 2002·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Andrew B AdamsKenneth A Newell
Mar 26, 2003·Cell Death and Differentiation·H WajantP Scheurich
Sep 2, 2003·Nature Reviews. Immunology·Bharat B Aggarwal
Sep 10, 2003·Journal of Leukocyte Biology·Rosa Maria AspalterHermann Maximilian Wolf
Sep 10, 2004·Current Molecular Medicine·Martin H Holtmann, Markus F Neurath
Jan 1, 2005·Rheumatology International·Paola CaramaschiLisa Maria Bambara
Sep 7, 2005·Current Opinion in Structural Biology·Ivet Bahar, A J Rader
Oct 8, 2005·Journal of Computational Chemistry·David Van Der SpoelHerman J C Berendsen
May 10, 2006·Proceedings of the National Academy of Sciences of the United States of America·Wenjun ZhengD Thirumalai
Aug 8, 2006·Biophysical Journal·Dmitry A KondrashovGeorge N Phillips
Aug 31, 2006·Bioinformatics·Barry J GrantLeo S D Caves
Feb 1, 2007·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Guo-Min Deng
Feb 28, 2007·Biopolymers·Sanbo Qin, Huan-Xiang Zhou
Jan 6, 2009·Journal of Molecular Biology·Riina TehverD Thirumalai
Sep 18, 2009·Advances in Experimental Medicine and Biology·Iqbal S Grewal
May 22, 2010·Nature Reviews. Drug Discovery·Denise Faustman, Miriam Davis
Sep 21, 2010·Molecular & Cellular Proteomics : MCP·Carlos R ReisRobbert H Cool
Oct 12, 2010·Nature Structural & Molecular Biology·Liwei WangHao Wu
Nov 18, 2010·Science Signaling·Yohei MukaiYasuo Tsutsumi
Apr 8, 2011·Bioinformatics·Ahmet BakanIvet Bahar

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Citations

Nov 28, 2012·Journal of the American Chemical Society·Aneesh ChandranSanjib Senapati

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Methods Mentioned

BETA
X-ray

Software Mentioned

STRIDE
pdbmat
ENM
GROMACS
PBSA
VMD
SETA
DSSP
Prody
MM

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