CARP interacts with titin at a unique helical N2A sequence and at the domain Ig81 to form a structured complex. Issue 18 (2nd September 2016)

• Record Type: Journal Article
• Authors: Zhou, Tiankun; Fleming, Jennifer R.; Franke, Barbara; Bogomolovas, Julius; Barsukov, Igor; Rigden, Daniel J.; Labeit, Siegfried; Mayans, Olga
• Is Part Of: FEBS letters. Volume 590:Issue 18(2016)
• Page Start: 3098
• Page End: 3110
• Publication Date: 2016-09-02
• Subjects: circular dichroism -- recombinant proteins -- SEC‐MALLS -- small‐angle X‐ray scattering -- X‐ray crystallography; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.12362
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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. Abstract :