# STRUCTURE AND FUNCTION OF TERMINAL COMPLEMENT PROTEINS

> **NIH NIH R01** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 1988 · $109,667

## Abstract

The objective of this project is to identify and define structural features
of terminal complement proteins which mediate their interactions with each
other and with target cell membranes during the cytolytic process.  This
will be accomplished through a detailed analysis of structure-function
relationships in the eighth component of human complement (C8).  Studies of
C8 interactions will focus on the final two steps leading to formation of
the cytolytic C5b-9 complex, namely C5b-7-C8-C5b-8-C9-C5b-9.  Evidence
suggests the alpha-gamma and beta subunits of C8 may be products of
different genes; therefore, initial experiments will examine the chemical
basis for the high affinity between these two proteins.  Subsequent
experiments will use chemical modifications to characterize structural
domains on beta which mediate interaction of C8 with C5b-7 while parallel
studies using chemical crosslinkers will attempt to define the C8 binding
site itself.  Other experiments will examine the C9 binding site on C5b-8
and by using chemical modifications, crosslinkers and synthetic C8-C9
dimers, attempt to define the role of C8 in mediating C9 incorporation into
this complex.  Regarding C8 interaction with target membranes, those
structural domains inserted in the lipid bilayer during lysis will be
identified using a photosensitive, membrane-restricted probe.
Intra-membrane peptides will be isolated and characterized to establish if
they contain extended sequences of hydrophobic residues analogous to
integral membrane proteins.  Occurrence of such sequences could explain the
mechanism by which these proteins function.  Concurrent with these studies,
amino acid sequencing of alpha, beta and gamma will be performed using
conventional methods and a parallel approach of oligonucleotide sequencing
of cloned cDNA inserts isolated from an existing human liver cDNA library.
With sequence information, highly specific oligonucleotide probes can be
prepared and used to begin long-term studies of alpha-gamma and beta gene
structure.  Availability of complete sequences will also contribute
substantially to defining structure-function correlates in C8.  Using
hepatocyte cell-cultures and cell-free systems, other experiments will
investigate the biosynthesis of C8.  These will focus on the existence of a
single-chain alpha-gamma precursor, the occurrence of pre- and pro-peptides
in alpha-gamma and beta, glycosylation and secretion of each and whether
association of subunits to form C8 is a pre- or post-secretory event.
Because this project is concerned with understanding the mechanism and
regulation of an intrinsic, physiological process for destroying cells, its
biological significance relates to potential improvements in the treatment
of infectious diseases and cancer.

## Key facts

- **NIH application ID:** 3126867
- **Project number:** 5R01AI016856-07
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **SAM.gov UEI:** J22LNTMEDP73
- **Principal Investigator:** JAMES M SODETZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $109,667
- **Award type:** 5
- **Project period:** 1982-07-01 → 1989-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126867

## Citation

> US National Institutes of Health, RePORTER application 3126867, STRUCTURE AND FUNCTION OF TERMINAL COMPLEMENT PROTEINS (5R01AI016856-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126867. Licensed CC0.

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