| http://purl.uniprot.org/citations/33647290 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33647290 | http://www.w3.org/2000/01/rdf-schema#comment | "Striated muscle responds to mechanical overload by rapidly up-regulating the expression of the cardiac ankyrin repeat protein, CARP, which then targets the sarcomere by binding to titin N2A in the I-band region. To date, the role of this interaction in the stress response of muscle remains poorly understood. Here, we characterise the molecular structure of the CARP-receptor site in titin (UN2A) and its binding of CARP. We find that titin UN2A contains a central three-helix bundle fold (ca 45 residues in length) that is joined to N- and C-terminal flanking immunoglobulin domains by long, flexible linkers with partial helical content. CARP binds titin by engaging an α-hairpin in the three-helix fold of UN2A, the C-terminal linker sequence, and the BC loop in Ig81, which jointly form a broad binding interface. Mutagenesis showed that the CARP/N2A association withstands sequence variations in titin N2A and we use this information to evaluate 85 human single nucleotide variants. In addition, actin co-sedimentation, co-transfection in C2C12 cells, proteomics on heart lysates, and the mechanical response of CARP-soaked myofibrils imply that CARP induces the cross-linking of titin and actin myofilaments, thereby increasing myofibril stiffness. We conclude that CARP acts as a regulator of force output in the sarcomere that preserves muscle mechanical performance upon overload stress."xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jmb.2021.166901"xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/author | "Chen J."xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/author | "Mayans O."xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/author | "Lange S."xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/author | "Zhou T."xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/author | "Ghassemian M."xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/author | "Bullard B."xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/author | "Kovermann M."xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/author | "Linke W.A."xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/author | "Fleming J.R."xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/author | "Biju A."xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/author | "Bogomolovas J."xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/author | "Borgeson E."xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/author | "Hessel A.L."xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/author | "Grundei D."xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/author | "Stronczek C."xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/name | "J Mol Biol"xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/pages | "166901"xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/title | "Molecular Characterisation of Titin N2A and Its Binding of CARP Reveals a Titin/Actin Cross-linking Mechanism."xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://purl.uniprot.org/core/volume | "433"xsd:string |
| http://purl.uniprot.org/citations/33647290 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/33647290 |
| http://purl.uniprot.org/citations/33647290 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/33647290 |