Crystal structure of interleukin-10 reveals the functional dimer with an unexpected topological similarity to interferon gamma

Structure
Alexander ZdanovAlexander Wlodawer

Abstract

Interleukin (IL)-10 is a cytokine that inhibits production of other regulatory factors, including interferon gamma (IFN-gamma) and IL-2. A dimer of IL-10 is present in solution and is presumed to participate in receptor binding, but the nature of the dimer has not been previously reported. An atomic model is necessary to interpret biological activity of IL-10 and to design mutants with agonistic or antagonistic properties. The X-ray crystal structure of a recombinant form of human IL-10 has been solved at 1.8 A resolution and refined to a crystallographic R-factor of 0.156. The molecule is a tight dimer made of two interpenetrating subunits, forming a V-shaped structure. Each half of the structure consists of a six alpha-helices, four originating from one subunit and two from the other. Four of the helices form a classical 'up-up-down-down' bundle observed in all other helical cytokines. The overall topology of the helices bears close resemblance to IFN gamma, although the similarity is less striking when examined in greater detail. The topological similarity of IL-10 to IFN gamma was totally unexpected, and may be a reflection of the close relationship between the biological effects of these two cytokines. The structure of IL-...Continue Reading

References

Feb 14, 1992·Biochemical and Biophysical Research Communications·F Q CunhaF Y Liew
Mar 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·F RoussetJ Banchereau
Sep 15, 1992·European Journal of Biochemistry·M FountoulakisG Garotta
Mar 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·R PiccoliG D'Alessio
Dec 1, 1991·The Journal of Experimental Medicine·C BogdanC Nathan
Feb 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·P VieiraK W Moore
Dec 1, 1989·The Journal of Experimental Medicine·D F FiorentinoT R Mosmann
Sep 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·S R Presnell, F E Cohen
Jan 1, 1985·Methods in Enzymology·W A Hendrickson
Dec 5, 1993·Journal of Molecular Biology·B LovejoyD Eisenberg
Jun 1, 1994·Protein Science : a Publication of the Protein Society·E DemchukR C Wade
Mar 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·G BlanchoC LeGuern
Jul 15, 1994·Biochemical and Biophysical Research Communications·R MasoodP S Gill
Mar 15, 1994·Structure·D A RozwarskiP A Karplus
Feb 11, 1994·Journal of Molecular Biology·M H UltschA M de Vos
Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·A S HoK W Moore
Jan 1, 1993·Annual Review of Immunology·K W MooreT R Mosmann
Sep 1, 1993·Protein Science : a Publication of the Protein Society·A WlodawerA Gustchina
Feb 1, 1993·The Journal of Experimental Medicine·P ChomaratP Miossec
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Jul 1, 1993·Acta Crystallographica. Section D, Biological Crystallography·L MazzarellaA Zagari
Jan 1, 1993·Acta Crystallographica. Section D, Biological Crystallography·K Y Zhang
Jul 17, 1992·Science·D B McKay

❮ Previous
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Citations

Dec 1, 1995·Protein Science : a Publication of the Protein Society·M J BennettD Eisenberg
Oct 1, 1996·Protein Science : a Publication of the Protein Society·A ZdanovA Wlodawer
May 6, 1998·Protein Science : a Publication of the Protein Society·U ReinekeJ Schneider-Mergener
May 1, 1996·Molecular Diversity·U ReinekeJ Schneider-Mergener
May 17, 2006·Journal of Biomedical Science·Chi-Chen WeiMing-Shi Chang
Dec 6, 2011·Immunologic Research·Takami SatoSenthamil R Selvan
May 4, 2004·International Immunopharmacology·Sergei V Kotenko, Jerome A Langer
May 4, 2004·International Immunopharmacology·Helmut Fickenscher, Heide Pirzer
May 4, 2004·International Immunopharmacology·Sunil ChadaAbner M Mhashilkar
May 8, 2004·Journal of Biotechnology·Rima MenassaJim Brandle
Aug 11, 2001·Current Opinion in Immunology·B E GewurzH L Ploegh
Jul 17, 1998·Current Opinion in Structural Biology·R B Russell, C P Ponting
Jan 20, 1998·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·I LalaniA R Ahmed
Dec 19, 2002·Cytokine & Growth Factor Reviews·Sergei V Kotenko
Apr 4, 2002·Trends in Immunology·Helmut FickenscherHeinrich Sticht
Feb 15, 2013·Biomacromolecules·Jugal DhandhukiaJ Andrew MacKay
Sep 1, 1995·Nature Structural Biology·R J Fletterick, J F Bazan
Oct 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·M KarpusasS Goelz
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·S V KotenkoS Pestka
Jun 14, 2012·The Journal of Biological Chemistry·Sung Il YoonMark R Walter
Jan 19, 2000·The Journal of Experimental Medicine·Y DingJ S Bromberg
Jan 7, 2003·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Naomi J LogsdonMark R Walter
Aug 5, 1999·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·R P DonnellyD S Finbloom
Jan 24, 2007·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·John B MummElizabeth A Grimm
Aug 18, 2010·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Hans Henrik GadRune Hartmann
Apr 9, 2008·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Brandi C JonesMark R Walter
May 22, 2002·Protein Science : a Publication of the Protein Society·Yanshun Liu, David Eisenberg
Feb 1, 1996·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·A I DenesyukT Korpela
Aug 17, 2012·Journal of Virology·Agus SunartoPeter J Walker
Mar 13, 2001·Annual Review of Immunology·K W MooreA O'Garra
Mar 23, 2004·Annual Review of Immunology·Sidney PestkaPaul B Fisher
Feb 23, 2012·Journal of Molecular Microbiology and Biotechnology·Christoph PöhlmannFlorian Gunzer
Jun 30, 2005·BMC Structural Biology·Sergei PletnevAlexander Zdanov
Nov 26, 2010·Human Genomics·Chad BrockerVasilis Vasiliou
Jul 23, 2013·PloS One·Oliver BraumHelmut Fickenscher
Feb 26, 2008·Folia Histochemica Et Cytobiologica·Aldona PietrzakDorota Krasowska
Jul 11, 2013·World Journal of Gastroenterology : WJG·Gareth J MarlowLynnette R Ferguson
May 31, 2014·Mediators of Inflammation·Piotr WojdasiewiczDariusz Szukiewicz

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