5K6P

The NMR structure of the m domain tri-helix bundle and C2 of human cardiac Myosin Binding Protein C

Summary for 5K6P

• Entry DOI: 10.2210/pdb5k6p/pdb
• NMR Information: BMRB: 30100
• Descriptor: Myosin-binding protein C, cardiac-type (1 entity in total)
• Functional Keywords: immunoglobulin, contractile protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 15497.70

Authors

Michie, K.A.,Kwan, A.H.,Tung, C.S.,Guss, J.M.,Trewhella, J. (deposition date: 2016-05-25, release date: 2016-11-09, Last modification date: 2024-05-15)

Primary citation

Michie, K.A.,Kwan, A.H.,Tung, C.S.,Guss, J.M.,Trewhella, J.
A Highly Conserved Yet Flexible Linker Is Part of a Polymorphic Protein-Binding Domain in Myosin-Binding Protein C.
Structure, 24:2000-2007, 2016

PubMed Abstract: The nuclear magnetic resonance (NMR) structure of the tri-helix bundle (THB) of the m-domain plus C2 (ΔmC2) of myosin-binding protein C (MyBP-C) has revealed a highly flexible seven-residue linker between the structured THB and C2. Bioinformatics shows significant patterns of conservation across the THB-linker sequence, with the linker containing a strictly conserved serine in all MyBP-C isoforms. Clinically linked mutations further support the functional significance of the THB-linker region. NMR, small-angle X-ray scattering, and binding studies show the THB-linker plus the first ten residues of C2 undergo dramatic changes when ΔmC2 binds Ca-calmodulin, with the linker and C2 N-terminal residues contributing significantly to the affinity. Modeling of all available experimental data indicates that the THB tertiary structure must be disrupted to form the complex. These results are discussed in the context of the THB-linker and the N-terminal residues of C2 forming a polymorphic binding domain that could accommodate multiple binding partners in the dynamic sarcomere.

PubMed: 27720588
DOI: 10.1016/j.str.2016.08.018

Experimental method

SOLUTION NMR