# MOLECULAR STRUCTURE OF THE ADENOVIRUS CAPSID

> **NIH NIH R01** · WISTAR INSTITUTE · 1993 · $414,082

## Abstract

The overall aim of the project is to determine the structure of the
adenovirus virion in atomic detail. A novel approach is mandated by its
large size (about 1000 Angstroms diameter) and the complicated arrangement
of its constituent 2700 polypeptides from 10 different protein species. The
virion will be investigated by combining information from an X-ray
crystallographic analysis of its major element, the coat protein hexon,
with information from electron microscopy. Hexon is a trimeric molecule
with three identical polypeptide chains of 967 residues (109,077 daltons
each). The crystal structure of hexon at 2.9 Angstrom resolution is being
refined by a combination of model-building using computer graphics,
restrained least-squares refinement, and molecular dynamics simulated
annealing methods to give a molecular model. The hexon structure will be
extended to the diffraction limit of about 2 Angstroms resolution and its
chemical characteristics analyzed in terms of charge, hydrogen bonding, and
hydropathy to discover the nature of hexon's extraordinary stability. A
unique structural feature in hexon, in which chains from different subunits
are entangled, indicates that topology can play an important role in
protein interactions.

The structure of the immunologically distinct type 5 hexon will be
determined, as will structures for hexons of types 40 and 41. Comparison of
hexons from different serotypes will reveal the structural basis for their
immunological differences and give the approximate location of antigenic
determinants, reveal how the viral coat has differentiated, and indicate
whether viral stability is correlated with type of illness. As hexon alone
is an effective vaccine when used in place of the potentially oncogenic
complete virus, short peptides could be used as cost-effective synthetic
vaccines against adenoviral infections in humans and domestic animals. High
resolution structures will permit exact modelling of interactions.

The large size of hexon and its distinctive shape permit its recognition in
electron micrographs of the virion and its fragments. This information has
been used to develop a model for the arrangement of the 240 hexons in the
capsid and to find relative positions of hexon molecules in two-dimensions
to about 1 Angstrom. Hexon now will be modelled into the capsid to study
hexon interactions in three-dimensions. Work aimed at understanding hexon's
internal stability will be extended to the capsid to explore hexon-hexon
interfaces and putative binding sites of a small protein that stabilizes
the capsid. These studies will lay the foundation for drugs designed to
disrupt the infective process by destabilizing or over-stabilizing the
capsid. The structural studies on adenovirus will serve as a model for
mammalian viruses and other complicated assemblies that are too large to be
amenable to crystallography alone. Study of these biological systems
requires an integration of investigative methods including electron
...

## Key facts

- **NIH application ID:** 3127098
- **Project number:** 5R01AI017270-14
- **Recipient organization:** WISTAR INSTITUTE
- **SAM.gov UEI:** DW1XZMGNFBL4
- **Principal Investigator:** ROGER M BURNETT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $414,082
- **Award type:** 5
- **Project period:** 1988-08-01 → 1995-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127098

## Citation

> US National Institutes of Health, RePORTER application 3127098, MOLECULAR STRUCTURE OF THE ADENOVIRUS CAPSID (5R01AI017270-14). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127098. Licensed CC0.

---

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