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Measurement clarifies role between protein structure and cell adhesion
James E. Kloeppel, Physical Sciences Editor
217-244-1073; kloeppel@illinois.edu
4/26/04
CHAMPAIGN, Ill. —
Scientists studying the adhesive properties of the neural cell adhesion
molecule (NCAM) – a protein that helps bind the nervous system
together – have found that two opposing models of cell adhesion
are both correct.
“Our extremely sensitive technique allows us to directly measure
how these proteins bind to one another, and to further explore the relationship
between their structure and function,” said Deborah Leckband,
a professor and head of chemical
and biomolecular engineering at the University of Illinois at Urbana-Champaign
and corresponding author of a paper to be published the week of April
26 in the Online Early Edition of the Proceedings of the National Academy
of Sciences.
Important in neural development and for linking muscles to neurons,
NCAM is a membrane-anchored protein that holds cells together through
bonds formed between five modular regions called domains. Previous studies
had generated two seemingly contradictory models for NCAM adhesion that
involved different domains.
To directly study the adhesive properties of NCAM, Leckband and her
colleagues used a surface-force apparatus to measure the molecular forces
between two NCAM monolayers as a function of the distance between them.
“Our direct-force measurements show that NCAM binds in two spatially
distinct configurations that result in different membrane separations,”
said Leckband, who also is a researcher at the university’s Beckman
Institute for Advanced Science and Technology. “The protein’s
modular architecture permits the formation of multiple bonds that engage
different modules, which allowed us to directly test both models.”
Previous studies of NCAM binding could detect only one or the other
configuration, Leckband said, thereby creating an apparent contradiction
between two opposing models. The researchers’ measurements confirm
both models, but disprove a recently proposed third model that was based
upon a recently published crystal structure.
“Many research groups rely on crystal structures to determine
the nature of chemical interactions that occur between the molecules
when they are bound,” Leckband said. “But we are finding
that, particularly for these weakly binding interactions, there are
other factors that influence how the crystal is formed that override
the physical interactions.”
By showing that NCAM forms either of two adhesive configurations, which
require different domains and span different membrane separations, the
researchers have reconciled several apparently contradictory experimental
results, and validated two of the current models as contributing to
spatially and molecularly distinct NCAM bonds.
“The different bonding configurations may serve as scaffolds that
hold the membranes apart and regulate the intercellular space,”
Leckband said. “The scaffolds would allow some molecules in –
like some proteins that activate the immune response – while excluding
others.”
Co-authors of the paper were graduate student Colin Johnson at the U.
of I., and Ichiro Fujimoto, Claire Perrin-Tricaud and Urs Rutishauser
at the Memorial Sloan-Kettering Cancer Center in New York City. The
National Institutes of Health funded the work.
