CARP interacts with titin at a unique helical N2A sequence and at the domain Ig81 to form a structured complex

• Verfasst von: Zhou, Tiankun [VerfasserIn]
• Verfasst von: Bogomolovas, Julius [VerfasserIn]
• Verfasst von: Labeit, Siegfried [VerfasserIn]
• Titel: CARP interacts with titin at a unique helical N2A sequence and at the domain Ig81 to form a structured complex
• Verf.angabe: Tiankun Zhou, Jennifer R. Fleming, Barbara Franke, Julius Bogomolovas, Igor Barsukov, Daniel J. Rigden, Siegfried Labeit and Olga Mayans
• E-Jahr: 2016
• Jahr: 2 September 2016
• Umfang: 13 S.
• Fussnoten: Gesehen am 21.09.2019 ; Available online 2 September 2016
• Titel Quelle: Enthalten in: Vereinigung der Europäischen Biochemischen GesellschaftenFEBS letters
• Ort Quelle: Chichester : Wiley, 1968
• Jahr Quelle: 2016
• Band/Heft Quelle: 590(2016), 18, Seite 3098-3110
• ISSN Quelle: 1873-3468
• DOI: doi:10.1002/1873-3468.12362
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: circular dichroism
• Sach-SW: recombinant proteins
• Sach-SW: SEC-MALLS
• Sach-SW: small-angle X-ray scattering
• Sach-SW: X-ray crystallography
• K10plus-PPN: 1586418769

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.