Skip to main content

Main menu

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons

User menu

  • Subscribe
  • Log in

Search

  • Advanced search
The Journal of Immunology
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons
  • Subscribe
  • Log in
The Journal of Immunology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Follow The Journal of Immunology on Twitter
  • Follow The Journal of Immunology on RSS

Identification of a Catalytic Exosite for Complement Component C4 on the Serine Protease Domain of C1s

Renee C. Duncan, Frida Mohlin, Deni Taleski, Theresa H. Coetzer, James A. Huntington, Richard J. Payne, Anna M. Blom, Robert N. Pike and Lakshmi C. Wijeyewickrema
J Immunol August 1, 2012, 1201085; DOI: https://doi.org/10.4049/jimmunol.1201085
Renee C. Duncan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Frida Mohlin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Deni Taleski
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Theresa H. Coetzer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James A. Huntington
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard J. Payne
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anna M. Blom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert N. Pike
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lakshmi C. Wijeyewickrema
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF
Loading

Abstract

The classical pathway of complement is crucial to the immune system, but it also contributes to inflammatory diseases when dysregulated. Binding of the C1 complex to ligands activates the pathway by inducing autoactivation of associated C1r, after which C1r activates C1s. C1s cleaves complement component C4 and then C2 to cause full activation of the system. The interaction between C1s and C4 involves active site and exosite-mediated events, but the molecular details are unknown. In this study, we identified four positively charged amino acids on the serine protease domain that appear to form a catalytic exosite that is required for efficient cleavage of C4. These residues are coincidentally involved in coordinating a sulfate ion in the crystal structure of the protease. Together with other evidence, this pointed to the involvement of sulfate ions in the interaction with the C4 substrate, and we showed that the protease interacts with a peptide from C4 containing three sulfotyrosine residues. We present a molecular model for the interaction between C1s and C4 that provides support for the above data and poses questions for future research into this aspect of complement activation.

Footnotes

  • This work was supported by a National Health and Medical Research Council of Australia Program Grant (490900 to R.N.P.) and the Swedish Research Council (K2009-68X-14928-06-3 to A.B.).

  • The online version of this article contains supplemental material.

  • Received April 12, 2012.
  • Accepted June 21, 2012.
  • Copyright © 2012 by The American Association of Immunologists, Inc.
Next
Back to top

In this issue

The Journal of Immunology: 208 (11)
The Journal of Immunology
Vol. 208, Issue 11
1 Jun 2022
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about The Journal of Immunology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Identification of a Catalytic Exosite for Complement Component C4 on the Serine Protease Domain of C1s
(Your Name) has forwarded a page to you from The Journal of Immunology
(Your Name) thought you would like to see this page from the The Journal of Immunology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Identification of a Catalytic Exosite for Complement Component C4 on the Serine Protease Domain of C1s
Renee C. Duncan, Frida Mohlin, Deni Taleski, Theresa H. Coetzer, James A. Huntington, Richard J. Payne, Anna M. Blom, Robert N. Pike, Lakshmi C. Wijeyewickrema
The Journal of Immunology August 1, 2012, 1201085; DOI: 10.4049/jimmunol.1201085

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Identification of a Catalytic Exosite for Complement Component C4 on the Serine Protease Domain of C1s
Renee C. Duncan, Frida Mohlin, Deni Taleski, Theresa H. Coetzer, James A. Huntington, Richard J. Payne, Anna M. Blom, Robert N. Pike, Lakshmi C. Wijeyewickrema
The Journal of Immunology August 1, 2012, 1201085; DOI: 10.4049/jimmunol.1201085
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Efficient Identification of Tembusu Virus CTL Epitopes in Inbred HBW/B4 Ducks Using a Novel MHC Class I–Restricted Epitope Screening Scheme
  • Poor-Quality Vβ Recombination Signal Sequences and the DNA Damage Response ATM Kinase Collaborate to Establish TCRβ Gene Repertoire and Allelic Exclusion
  • Multifaceted Activities of Seven Nanobodies against Complement C4b
Show more MOLECULAR AND STRUCTURAL IMMUNOLOGY

Similar Articles

Navigate

  • Home
  • Current Issue
  • Next in The JI
  • Archive
  • Brief Reviews
  • Pillars of Immunology
  • Translating Immunology

For Authors

  • Submit a Manuscript
  • Instructions for Authors
  • About the Journal
  • Journal Policies
  • Editors

General Information

  • Advertisers
  • Subscribers
  • Rights and Permissions
  • Accessibility Statement
  • FAR 889
  • Privacy Policy
  • Disclaimer

Journal Services

  • Email Alerts
  • RSS Feeds
  • ImmunoCasts
  • Twitter

Copyright © 2022 by The American Association of Immunologists, Inc.

Print ISSN 0022-1767        Online ISSN 1550-6606