Key result
CARP interacts with titin at a unique helical N2A sequence (UN2A) and the Ig81 domain to form a structured complex, revealing that UN2A has a stable alpha-helical fold.
No direct clinical application yet; extends structural models of titin-CARP binding but leaves functional roles open.
The cardiac ankyrin repeat protein (CARP) is up-regulated in the myocardium during cardiovascular disease and in response to mechanical or toxic stress. Stress-induced CARP interacts with the N2A spring region of the titin filament to modulate muscle compliance. We characterize the interaction between CARP and titin-N2A and show that the binding site in titin spans the dual domain UN2A-Ig81. We find that the unique sequence UN2A is not structurally disordered, but that it has a stable, elongated α-helical fold that possibly acts as a constant force spring. Our findings portray CARP/titin-N2A as a structured node and help to rationalize the molecular basis of CARP mechanosensing in the sarcomeric I-band.
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Zhou et al. (2016) studied this question. Recombinant CARP and titin N2A proteins was evaluated on Protein-protein interaction and structural characterization. CARP interacts with titin at a unique helical N2A sequence (UN2A) and the Ig81 domain to form a structured complex, revealing that UN2A has a stable alpha-helical fold.
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