Solution structure of Compstatin, a potent complement inhibitor

Protein Science : a Publication of the Protein Society
Dimitrios MorikisJohn D Lambris

Abstract

The third component of complement, C3, plays a central role in activation of the classical, alternative, and lectin pathways of complement activation. Recently, we have identified a 13-residue cyclic peptide (named Compstatin) that specifically binds to C3 and inhibits complement activation. To investigate the topology and the contribution of each critical residue to the binding of Compstatin to C3, we have now determined the solution structure using 2D NMR techniques; we have also synthesized substitution analogues and used these to study the structure-function relationships involved. Finally, we have generated an ensemble of a family of solution structures of the peptide with a hybrid distance geometry-restrained simulated-annealing methodology, using distance, dihedral angle, and 3J(NH-Halpha)-coupling constant restraints. The Compstatin structure contained a type I beta-turn comprising the segment Gln5-Asp6-Trp7-Gly8. Preference for packing of the hydrophobic side chains of Val3, Val4, and Trp7 was observed. The generated structure was also analyzed for consistency using NMR parameters such as NOE connectivity patterns, 3J(NH-Halpha)-coupling constants, and chemical shifts. Analysis of Ala substitution analogues suggested t...Continue Reading

References

Oct 1, 1977·Journal of Pharmaceutical Sciences·B J Johnson
Sep 15, 1977·Journal of Molecular Biology·P Y Chou, G D Fasman
Jul 1, 1992·The Journal of Hospital Infection·B Nyström
Jan 1, 1992·Journal of Biomolecular NMR·J KuszewskiA T Brünger
Jan 1, 1992·Clinical Neuropharmacology·L F GramK K Nielsen
Sep 1, 1991·Immunology Today·M M Frank, L F Fries
Jan 1, 1991·Annual Review of Biophysics and Biophysical Chemistry·H J Dyson, P E Wright
Nov 20, 1991·Journal of Molecular Biology·D S WishartF M Richards
Jan 1, 1990·Current Topics in Microbiology and Immunology·T E Hugli
Jan 1, 1985·Advances in Protein Chemistry·G D RoseJ A Smith
Sep 5, 1988·Journal of Molecular Biology·C M Wilmot, J M Thornton
May 5, 1988·Journal of Molecular Biology·H J DysonR A Lerner
Feb 14, 1971·Journal of Molecular Biology·B Lee, F M Richards
Jan 1, 1980·Journal of Immunopharmacology·A M Reynard
Dec 16, 1983·Biochemical and Biophysical Research Communications·M RanceK Wüthrich
Jan 1, 1981·Advances in Protein Chemistry·J S Richardson
Dec 1, 1995·The Journal of Experimental Medicine·M EggersU H Koszinowski
May 1, 1994·The Journal of Investigative Dermatology·S G el-LatiM K Church
Jan 1, 1995·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·H J Dyson, P E Wright
Apr 1, 1994·European Journal of Clinical Investigation·B P Morgan
Jan 1, 1994·Springer Seminars in Immunopathology·K B Reid, M W Turner
Jan 1, 1994·Springer Seminars in Immunopathology·K R KalliD T Fearon
Apr 1, 1994·Cardiovascular Research·K S KilgoreB R Lucchesi
Mar 1, 1993·Biological Mass Spectrometry·W T Moore
Dec 1, 1996·Journal of Biomolecular NMR·R A LaskowskiJ M Thornton
Jan 1, 1996·Microbiology and Immunology·M Matsushita
Jul 1, 1963·Journal of Molecular Biology·G N RAMACHANDRANV SASISEKHARAN

❮ Previous
Next ❯

Citations

Jul 25, 2000·Immunopharmacology·A Sahu, J D Lambris
Sep 22, 1998·Nature Biotechnology·A Persidis
Oct 3, 2001·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·S K Shernan, C D Collard
Mar 21, 2002·Fundamental & Clinical Pharmacology·T MonsinjonM Fontaine
Dec 7, 2007·Bioorganicheskaia khimiia·L V KozlovA P Kaplun
Oct 6, 2007·Expert Opinion on Biological Therapy·Ming Zhang, Michael C Carroll
Mar 29, 2011·Progress in Retinal and Eye Research·Kyoko Ohno-Matsui
May 15, 2007·Journal of Molecular Graphics & Modelling·Phanourios TamamisGeorgios Archontis
Oct 29, 2005·Scandinavian Journal of Immunology·J O GrönroosV J O Laine
Aug 7, 2009·Journal of Molecular Recognition : JMR·Paola MagottiJohn D Lambris
Oct 11, 2008·Chemical Biology & Drug Design·Ting-Lan ChiuYiannis N Kaznessis
Jan 12, 2012·Chemical Biology & Drug Design·Phanourios TamamisGeorgios Archontis
Mar 1, 2011·Chemical Biology & Drug Design·Aliana López de VictoriaDimitrios Morikis
Feb 13, 2010·Xenotransplantation·Shuji MiyagawaMasahiro Fukuzawa
Mar 9, 2005·Biophysical Chemistry·Mee Kyung SongJooyoung Lee
Jan 13, 2006·Protein Expression and Purification·Madan Katragadda, John D Lambris
Jul 14, 2005·Molecular Immunology·Tom E Mollnes, Michael Kirschfink
Oct 6, 2009·Molecular Immunology·Hongchang QuJohn D Lambris
Aug 2, 2011·Journal of Molecular Biology·Longguang JiangPeter A Andreasen
Jun 18, 2015·Frontiers in Immunology·Nicolas S MerleLubka T Roumenina
May 21, 2010·Biophysical Journal·M L BellowsD Morikis
May 26, 2004·Molecular Immunology·D MastellosJ D Lambris
Sep 1, 2006·Expert Review of Clinical Immunology·T Sakari Jokiranta
Jul 11, 2013·Current Opinion in Organ Transplantation·Lubka T RoumeninaVéronique Frémeaux-Bacchi
Dec 8, 2000·ASAIO Journal : a Peer-reviewed Journal of the American Society for Artificial Internal Organs·J Janatova
Feb 14, 2018·Journal of Thrombosis and Haemostasis : JTH·E W SkjefloT E Mollnes
Feb 7, 2018·Expert Opinion on Drug Discovery·Yijun Huang
Oct 19, 2004·The Journal of Biological Chemistry·Madan KatragaddaJohn D Lambris
Feb 16, 2002·The Journal of Biological Chemistry·Dimitrios MorikisJohn D Lambris
Aug 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·A SahuJ D Lambris
Jul 6, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·A SandovalR T Ogata
Jan 25, 2003·Critical Care Medicine·Deepak Bhole, Gregory L Stahl
Aug 6, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alfred H J KimPeter D Katsikis

❮ 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.