C1q and Mannose-Binding Lectin Interact with CR1 in the Same Region on CCP24-25 Modules

Front Immunol. 2018 Mar 7:9:453. doi: 10.3389/fimmu.2018.00453. eCollection 2018.

Abstract

Complement receptor type 1 (CR1) is a multi modular membrane receptor composed of 30 homologous complement control protein modules (CCP) organized in four different functional regions called long homologous repeats (LHR A, B, C, and D). CR1 is a receptor for complement-opsonins C3b and C4b and specifically interacts through pairs of CCP modules located in LHR A, B, and C. Defense collagens such as mannose-binding lectin (MBL), ficolin-2, and C1q also act as opsonins and are involved in immune clearance through binding to the LHR-D region of CR1. Our previous results using deletion variants of CR1 mapped the interaction site for MBL and ficolin-2 on CCP24-25. The present work aimed at deciphering the interaction of C1q with CR1 using new CR1 variants concentrated around CCP24-25. CR1 bimodular fragment CCP24-25 and CR1 CCP22-30 deleted from CCP24-25 produced in eukaryotic cells enabled to highlight that the interaction site for both MBL and C1q is located on the same pair of modules CCP24-25. C1q binding to CR1 shares with MBL a main common interaction site on the collagen stalks but also subsidiary sites most probably located on C1q globular heads, contrarily to MBL.

Keywords: C1q; CCP modules; CR1/CD35; complement; interaction; protein engineering; receptor; surface plasmon resonance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Complement C1q / chemistry*
  • Complement C1q / genetics
  • Complement C1q / immunology
  • Ficolins
  • Humans
  • Lectins / chemistry
  • Lectins / genetics
  • Lectins / immunology
  • Mannose-Binding Lectin / chemistry*
  • Mannose-Binding Lectin / genetics
  • Mannose-Binding Lectin / immunology
  • Peptides / chemistry*
  • Peptides / genetics
  • Peptides / immunology
  • Protein Binding
  • Protein Domains
  • Protein Structure, Secondary
  • Receptors, Complement 3b / chemistry*
  • Receptors, Complement 3b / genetics
  • Receptors, Complement 3b / immunology

Substances

  • Lectins
  • Mannose-Binding Lectin
  • Peptides
  • Receptors, Complement 3b
  • Complement C1q