ARTICLES
A Decoded Stretchy Molecule gives Living Tissues Flexibility
By Rachel Fergus
Researchers reveal the atomic structure of
tropoelastin
The stretchiness that allows living tissues to expand, contract,
stretch, and bend throughout a lifetime is the result of a protein
molecule called tropoelastin. Remarkably, this molecule can
stretch to eight times its length, always returning to its original
size.
Researchers have decoded the molecular structure of
tropoelastin, a protein that gives living tissues the ability to
stretch and retract, and detailed how its structure is altered
in various genetically-driven diseases.
Tropoelastin is the precursor molecule of elastin which, along
with structures called microfibrils, is the key to flexibility of tissues
including skin, lungs, and blood vessels. But the molecule is
complex, made up of 698 amino acids in sequence and filled
with disordered regions. Unravelling its structure has been a
major challenge.
Using a combination of molecular modeling and experimental
observation to build up an atom-by-atom picture of the molecule’s
structure, researchers from the University of Sydney, MIT and
University of Manchester have now decoded the molecular
structure of this complex molecule.
Published in June in the Proceedings of the National Academy of
Sciences, the research also identifies what can go wrong with its
structure in various genetically driven diseases.
Author and postdoctoral researcher Anna Tarakanova, from the
School of Engineering at Massachusetts Institute of Technology
(MIT), said the structure of tropoelastin had been elusive until
now.
“Traditional characterisation methods are insufficient for decoding
this molecule because it’s very large, disordered and dynamic,”
she said. “However the combination of computer modeling and
experimental observations used allowed us to predict a fully
atomistic structure of the molecule.”
The study showed how certain disease-causing mutations in
the gene that controls the formation of tropoelastin change the
molecule’s stiffness and dynamic responses, which could help in
the design of treatments or countermeasures for these conditions.
‘Artificial’ mutations induced by the researchers can be used to
better understand the function of the specific part of the gene
affected by that mutation. The study also looked at the specific
changes in the tropoelastin molecule caused by mutations
associated with known diseases, such as cutis laxa, in which the
skin lacks elasticity and hangs loosely.
This diagram depicts the configuration of the complex
tropoelastin molecule, which forms the basis for the elastin that
gives tissues like skin and blood vessels their elasticity. The
molecule’s atom-by-atom structure was decoded by a team of
researchers from Australia the US and the UK. Credit courtesy
of the researchers.
Co-author Professor Anthony Weiss, the University of Sydney’s
McCaughey Chair in Biochemistry, from the Faculty of Science
and multidisciplinary Charles Perkins Centre, said the techniques
used to unravel the structure of topoelastin were powerful. “This
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SCIENCE EDUCATIONAL NEWS VOL 67 NO 3