# STRUCTURAL BASIS OF C3 FUNCTIONS

> **NIH NIH R01** · SCRIPPS CLINIC AND RESEARCH FOUNDATION · 1988 · $193,010

## Abstract

The third component of complement, C3, is an important participant in
immune surveillance and immune response pathways.  Activation of the
complement system by the classical or alternative pathways results in a and
controlled fragmentation of the C3 molecule.  Interactions of C3 fragments
with cell surface receptors serve to modulate complement-dependent
granulocyte and lymphocyte functions.  The elucidation of molecular
features germane to these complement functions will require (1) further
characterization of the structure of the individual C3 subdomains involved,
and (2) an evaluation of the physiochemical basis for their binding
properties.  At the structural level, our objective will be to complete the
primary structure of C3 both by limited protein sequence analysis of the
major cyanogen bromide fragments and also by full sequence analysis of
cloned cDNA encoding the C3 molecule.  Once human C3 cDNA clones are
identified in a human cDNA library, the emphasis will shift from mouse to
human.  This combined approach, whereby limited protein sequence data is
primarily used to confirm the isolation of specific cDNA clones and to
insure proper reading frame assignments, has the potential to shorten by
several years the time required to establish the complete primary structure
of C3.  Furthermore, the structure of C3 from two species (mouse and human)
will be compared in order to determine the structural correlates for
specific functional domains of the molecule.  We have recently identified a
unique thiolester bond in C3 which is strictly required for the hemolytic
function of this molecule.  We propose to delineate the biosynthetic
pathway(s) for formation of the thiolester bond, determine the mechanism
whereby the acyl component of the thiolester is transferred to acceptor
molecules with formation of a covalent bond, and study further examples of
thiolester-containing proteins of eukarocyte origin.  The major
transforming antigen of simian virus 40 is a major candidate.  Stable cell
receptor binding sites have been shown to be associated with several
subdomain structures of C3 (i.e. C3b, iC3b, C3d, and C3c).  We propose to
develop direct binding assays for the C3 receptors, CR2 and CR3, and
identify, by inhibition studies, peptides from the major subdomains of C3
which retain specific receptor binding activity.  These peptides may have
specific application as inhibitors of in vivo C3 receptor interactions,
have the potential of offering a new class of inhibitors to the processes
involved in inflammatory reactions.

## Key facts

- **NIH application ID:** 3128579
- **Project number:** 5R01AI019222-07
- **Recipient organization:** SCRIPPS CLINIC AND RESEARCH FOUNDATION
- **Principal Investigator:** BRIAN F TACK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $193,010
- **Award type:** 5
- **Project period:** 1981-12-01 → 1989-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128579

## Citation

> US National Institutes of Health, RePORTER application 3128579, STRUCTURAL BASIS OF C3 FUNCTIONS (5R01AI019222-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128579. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*