# STRUCTURE - ACTIVITY STUDIES OF COMPLEMENT PROTEIN C9

> **NIH NIH R01** · UNIVERSITY OF MISSOURI KANSAS CITY · 1992 · $286,420

## Abstract

The ninth component of complement (C9) is responsible for the cytotoxic
action of complement. It is, therefore, an important component of the
immune system. C9 is a 70 Kda glycoproteins which in order to be
effective must change from a stably folded, water soluble protein into
an intrinsic membrane protein. The nature of this transformation must be
understood to appreciate how this protein functions. To gain such
information a thorough investigation of the structure C9 in its native
water soluble form and in its membrane bound form will be initiated.
Information static structures will be obtained by surface mapping, EPR
and fluorescence spectroscopy, electron microscopy and 3-D image
reconstruction, and small angle neutron scattering. The kinetics of
structural changes as they occur when the protein enters a membrane will
be followed by EPR and fluorescence spectroscopy. All techniques will
benefit from labeling of the protein with specific probes. In the past
specific labeling was limited by the small number of sites available on
a protein. However, this problem can now be circumvented to some extend
by site-directed mutagenesis and the use of newer spectroscopic
techniques of sufficient sensitivity to examine small amounts of mutant
proteins. The approach is to employ genetically engineered labeling
sites in the C9 sequence for the attachment of labels.

The specific aims for the next grant period are:

1. To identify the peptide region necessary for hemolytic function by
generation of C9 mutants with free cysteines for site-specific
attachment of labels, and of hybrid molecules composed of segments from
lytic (human) and non-lytic (horse) C9 molecules.

2. To determine the presence (or absence) of transmembrane regions in
membrane-bound C9 by mapping of the surfaces of native C9 and membrane-
bound C9 with immunologic, enzymatic and spectroscopic methods.

3. To identify contact sites between C8 and C9 and to measure the
kinetics of C9 refolding and insertion into membranes.

4. To generate a low resolution structure of membrane-bound C9 by 3-
dimensional image reconstruction and by small angle neutron scattering
combined with contrast variation procedures.

## Key facts

- **NIH application ID:** 3128819
- **Project number:** 2R01AI019478-11
- **Recipient organization:** UNIVERSITY OF MISSOURI KANSAS CITY
- **SAM.gov UEI:** J9CDGR596MN3
- **Principal Investigator:** ALFRED F ESSER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $286,420
- **Award type:** 2
- **Project period:** 1982-04-01 → 1997-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128819

## Citation

> US National Institutes of Health, RePORTER application 3128819, STRUCTURE - ACTIVITY STUDIES OF COMPLEMENT PROTEIN C9 (2R01AI019478-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128819. Licensed CC0.

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