Investigating the role of aB-crystallin in controlling heart muscle stiffness

We have shown a direct interaction between titin domains and the molecular chaperone alphaB-crystallin that confers significant stiffness on cardiac muscle fibres. We have pinpointed this effect to short amino-acid segment of alphaB-crystallin. A dilated cardiomyopathy-causing mutation in this region of alphaB-crystallin significantly attenuates this stabilisation. These results are novel and exciting, as they for the first time provide concrete evidence for the specific region of B that is responsible for binding titin. We are still working on determining the atomic structure of the alphaB-crystallin:titin interaction, and to investigate its associated dynamics. The anticipated atomic resolution characterisation of the interaction will, together with our insights from functional assays on cardiac muscle fibres, will provide the necessary proof-of-principle data for longer-term grants and ultimately novel therapeutic approaches that will target the alphaB-crystallin:titin interaction.

Publication linked to this award:

1. Cameron W. Turtle, Georg Hochberg, Henrik Müller, Katja Gehmlich, Andrew Baldwin, Charles Redwood, Justin Benesch. alphaB-Crystallin Binds to Titin Ig Domains and Increases Stiffness of Skinned Cardiac Trabeculae Biophysical Journal 2015, Vol. 108, Issue 2, p444a