# STRUCTURE AND INTERACTION OF PROTEINS WITH MEMBRANES

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 1992 · $190,595

## Abstract

Cell surface carbohydrates are involved in cellular recognition and serve
as receptors for viruses, antibodies, toxins and hormones.  The aim of
these studies is to define a structural basis for the biochemical
mechanisms that govern carbohydrate mediated cellular processes such as
viral infectivity, immune response and cell differentiation (or
malignancy).  The stringent sugar specificity of lectins and their
ability to mimic normal cellular function has been exploited as one
approach to study determinants of receptor stimulation.  Thus, structural
knowledge on the atomic level is essential to understand the
stereochemical requirements for their sugar specificity.

We are extending our studies of the crystal complex of wheat germ
agglutinin (WGA1) and the T-5 sialoglycopeptide (derived from its
receptor glycophorin A), which revealed 2 new sites for binding sialic
acid (NeuNAc), one of the most common cell surface target sugars.
Structure refinement will be completed and this structure compared with
that of native WGA1 to determine the effect of asymmetric sugar binding
(only 3 of the 8 possible sites occupied) and inter-dimer crosslinkage
on subunit/subunit association.  In addition, we shall use recombinant
techniques, NMR and x-ray crystallography to define differential fine-
specificities for NeuNAc and GlcNAc at each of the four unique
heterogeneous binding sites and design and clone a domain with a binding
site of optimal affinity for NeuNAc and GlcNAc.

We shall determine the 2.5 Angstroms structure of snowdrop lectin (GNA),
a potent inhibitor of human and simian immunodeficiency viruses.  GNA is
alpha-Man specific (-Man-alpha1,3)Man-) and represents a new lectin
family distinct from the Man/Glc specific legume family.  The structure
will be determined for the mono-saccharide complex by MIR methods at 2.5
Angstroms resolution, using four heavy atom derivatives, and for the Me-
Man-alpha1,3-Man complex (different crystal form) by molecular
replacement.

To understand the mechanisms underlying molecular sorting in the plant,
we propose to determine the crystal structure of barley lectin precursor
by molecular replacrment techniques.  This pro-protein contains 15
additional amino acids at its carboxyl terminus (as does pro-WGA), needed
for correct deposition of mature lectin in the vacuoles.  The folding
motif of this C-terminal domain is believed to be the key to correct
targeting.

To further define the role a WGA-domain plays as a single unit in binding
chito-oligosaccharides in vivo, structural studies will be initiated with
tobacco chitinase, a monomeric anti-fungal hydrolase that acts on chitin
to produce GlcNAc disaccharides, utilizing a WGA-like domain for binding
at its N-terminus.

## Key facts

- **NIH application ID:** 3127602
- **Project number:** 2R01AI017992-12
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **SAM.gov UEI:** MLQFL4JSSAA9
- **Principal Investigator:** CHRISTINE S WRIGHT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $190,595
- **Award type:** 2
- **Project period:** 1980-09-01 → 1997-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127602

## Citation

> US National Institutes of Health, RePORTER application 3127602, STRUCTURE AND INTERACTION OF PROTEINS WITH MEMBRANES (2R01AI017992-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127602. Licensed CC0.

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