Crystal structures of the pro-inflammatory cytokine interleukin-23 and its complex with a high-affinity neutralizing antibody

Journal of Molecular Biology
Brian M BeyerPeter Orth

Abstract

Interleukin (IL)-23 is a pro-inflammatory cytokine playing a key role in the pathogenesis of several autoimmune and inflammatory diseases. We have determined the crystal structures of the heterodimeric p19-p40 IL-23 and its complex with the Fab (antigen-binding fragment) of a neutralizing antibody at 2.9 and 1.9 A, respectively. The IL-23 structure closely resembles that of IL-12. They share the common p40 subunit, and IL-23 p19 overlaps well with IL-12 p35. Along the hydrophilic heterodimeric interface, fewer charged residues are involved for IL-23 compared with IL-12. The binding site of the Fab is located exclusively on the p19 subunit, and comparison with published cytokine-receptor structures suggests that it overlaps with the IL-23 receptor binding site.

References

May 2, 1998·The EMBO Journal·J BravoE Y Jones
Jan 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jun YinPeter G Schultz
Jun 28, 2003·Science·Martin J BoulangerK Christopher Garcia
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Nov 18, 2004·Immunological Reviews·Claire L LangrishDaniel J Cua
Nov 18, 2004·Immunological Reviews·Wendy T WatfordJohn J O'Shea
Jan 20, 2005·The Journal of Experimental Medicine·Claire L LangrishDaniel J Cua
Jun 28, 2005·Nucleic Acids Research·Jens Kleinjung, Franca Fraternali
Feb 24, 2006·Proceedings of the National Academy of Sciences of the United States of America·Taro TamadaRyota Kuroki
May 4, 2006·The Journal of Clinical Investigation·Yi ChenDaniel J Cua
May 12, 2006·Nature·John L LangowskiMartin Oft

❮ Previous
Next ❯

Citations

May 10, 2011·Immunologic Research·Lindsay L Jones, Dario A A Vignali
Jul 21, 2012·Nature Immunology·Dario A A Vignali, Vijay K Kuchroo
Sep 8, 2011·Infection and Immunity·Marije OostingLeo A B Joosten
Nov 29, 2013·Immunotherapy·Qingdong GuanZhikang Peng
Oct 31, 2014·Nature Communications·Johan DesmetSavvas N Savvides
Apr 17, 2012·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Takumi ShirouzonoShinji Ikemizu
Jul 24, 2015·Proceedings of the National Academy of Sciences of the United States of America·Veronica C CasinaX Long Zheng
Jun 24, 2015·Protein Science : a Publication of the Protein Society·Brigitte MaurerCharles Eigenbrot
Apr 12, 2011·New Biotechnology·Jo Erika T NarcisoEduardo A Padlan
Nov 3, 2011·Immunology·Chunlei TangWenlong Huang
Apr 27, 2010·Scandinavian Journal of Immunology·A Paradowska-GoryckaS Maslinski
Dec 18, 2009·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Mar 19, 2014·Immunology·W Mark AbbottDavid C Lowe
Aug 15, 2015·Protein Engineering, Design & Selection : PEDS·Karin StenderupKenneth H Grabstein
Feb 14, 2012·Structure·Vidhyashankar RamamurthySteven Sheriff
Aug 22, 2013·Cytokine & Growth Factor Reviews·Sanjay SwaminathanTomozumi Imamichi
Dec 11, 2014·Annual Review of Immunology·Jamie B SpanglerK Christopher Garcia
Oct 20, 2011·Vaccine·Rojo Anthony RatsimandresyMarie-Christophe Boissier
Aug 10, 2010·Journal of Molecular Biology·Jinquan LuoJacqueline Benson
Jun 9, 2016·Protein Engineering, Design & Selection : PEDS·Andrew C R Martin, Anthony R Rees
Nov 28, 2018·Journal of Receptor and Signal Transduction Research·Noor Saba KhanArun Kumar Jain
Aug 5, 2017·Expert Opinion on Drug Discovery·Glenn R MassonJohn E Burke
Oct 27, 2012·British Journal of Cancer·H J M A A ZijlmansA Gorter
Nov 8, 2019·Proteins·Justas DapkūnasČeslovas Venclovas
Jun 11, 2020·The Journal of Biological Chemistry·Alessandra EschDoreen M Floss
May 30, 2021·Developmental and Comparative Immunology·Lusheng XinLinsheng Song

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.