Citation: Clair Baldock, Andres F Oberhauser, Liang Ma, Donna Lammie, Veronique Siegler, Suzanne M Mithieux, Yidong Tu, John Yuen Ho Chow, Farhana Suleman, Marc Malfois, Sarah Rogers, Liang Guo, Thomas C Irving, Tim J Wess, Anthony S Weiss,
(2011)
Shape of tropoelastin, the highly extensible protein that controls human tissue elasticity. Proceedings of the National Academy of Sciences of the United States of America 108(11): Full text doi:10.1073/pnas.1014280108
Shapes of full-length tropoelastin calculated from solution X-ray (SAXS) or neutron (SANS) scattering data. An overlay of the models from the two methods is also shown. The proposed locations of the N-terminus, the spur region containing exons 20-24 and the C-terminus are indicated. Scale bar is 5 nm.
Elastin dominates the mass of the aorta where it encounters the peaks and troughs of systole and diastole over the course of two billion heartbeats in a lifetime. Tropoelastin is the soluble precursor to elastin, which is constructed by the hierarchical assembly and cross-linking of many tropoelastin monomers. Tropoelastin has a half-life of more than 70 years therefore providing a durable material that is intended to elastically serve until old age. Consequences of elastolytic damage in aortic aneurysms, emphysema and solar elastosis confirm the key roles of elastin in tissue function. Despite its biological importance, little is known of the shape and assembly mechanism of tropoelastin as its unique composition and propensity to self-associate has hampered structural studies. In order to shed light on the structure of tropoelastin, we used small angle X-ray and neutron scattering to solve the nanostructure of full-length and corresponding overlapping fragments of tropoelastin allowing us to identify discrete regions of the molecule. We have found that tropoelastin is an asymmetric molecule with a gradual coil along the long, spring-like axis of the molecule. This coil region accounts for most of the elasticity of tropoelastin. The spur region protruding from the side of the molecule corresponds to a predicted hinge region containing exons 20-24. Beyond the spur there is a bridge to the C-terminal region. The tropoelastin molecule terminates in a more compact “foot-like” region. This part of the molecule includes the cell-interactive C-terminus of tropoelastin. We also showed that individual tropoelastin molecules are highly extensible yet elastic without hysteresis to perform as highly efficient molecular nanosprings. In summary, structural analysis reveals two dominant, functionally relevant parts of the molecule: the coil which contributes to elasticity and the foot that encompasses the C-terminal cell contact region. Our findings shed light on how biology uses this single protein to build durable elastic structures that allow for cell attachment to an appended foot.
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