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TitleA Highly Conserved Yet Flexible Linker Is Part of a Polymorphic Protein-Binding Domain in Myosin-Binding Protein C.
Journal, issue, pagesStructure, Vol. 24, Issue 11, Page 2000-2007, Year 2016
Publish dateNov 1, 2016
AuthorsKatharine A Michie / Ann H Kwan / Chang-Shung Tung / J Mitchell Guss / Jill Trewhella /
PubMed AbstractThe 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 ...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.
External linksStructure / PubMed:27720588
MethodsSAS (X-ray synchrotron) / NMR (solution)
Structure data

SASDDD9:
Cardiac myosin binding protein C: tri-helix bundle from the motif with C2 domain
Method: SAXS/SANS

PDB-5k6p:
The NMR structure of the m domain tri-helix bundle and C2 of human cardiac Myosin Binding Protein C
Method: SOLUTION NMR

Source
  • Human sequence obtained using e. coli expression
  • homo sapiens (human)
KeywordsCONTRACTILE PROTEIN / immunoglobulin

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