2LHU

Structural Insight into the Unique Cardiac Myosin Binding Protein-C Motif: A Partially Folded Domain

Summary for 2LHU

• Entry DOI: 10.2210/pdb2lhu/pdb
• NMR Information: BMRB: 17867
• Descriptor: Mybpc3 protein (1 entity in total)
• Functional Keywords: cardiac, structural protein
• Biological source: Mus musculus (mouse)
• Total number of polymer chains: 1
• Total formula weight: 13997.66

Authors

Howarth, J.W.,Rosevear, P.R.,Ramisetti, S.,Nolan, K.,Sadayappan, S. (deposition date: 2011-08-18, release date: 2012-01-11, Last modification date: 2024-05-01)

Primary citation

Howarth, J.W.,Ramisetti, S.,Nolan, K.,Sadayappan, S.,Rosevear, P.R.
Structural Insight into Unique Cardiac Myosin-binding Protein-C Motif: A PARTIALLY FOLDED DOMAIN.
J.Biol.Chem., 287:8254-8262, 2012

PubMed Abstract: The structural role of the unique myosin-binding motif (m-domain) of cardiac myosin-binding protein-C remains unclear. Functionally, the m-domain is thought to directly interact with myosin, whereas phosphorylation of the m-domain has been shown to modulate interactions between myosin and actin. Here we utilized NMR to analyze the structure and dynamics of the m-domain in solution. Our studies reveal that the m-domain is composed of two subdomains, a largely disordered N-terminal portion containing three known phosphorylation sites and a more ordered and folded C-terminal portion. Chemical shift analyses, d(NN)(i, i + 1) NOEs, and (15)N{(1)H} heteronuclear NOE values show that the C-terminal subdomain (residues 315-351) is structured with three well defined helices spanning residues 317-322, 327-335, and 341-348. The tertiary structure was calculated with CS-Rosetta using complete (13)C(α), (13)C(β), (13)C', (15)N, (1)H(α), and (1)H(N) chemical shifts. An ensemble of 20 acceptable structures was selected to represent the C-terminal subdomain that exhibits a novel three-helix bundle fold. The solvent-exposed face of the third helix was found to contain the basic actin-binding motif LK(R/K)XK. In contrast, (15)N{(1)H} heteronuclear NOE values for the N-terminal subdomain are consistent with a more conformationally flexible region. Secondary structure propensity scores indicate two transient helices spanning residues 265-268 and 293-295. The presence of both transient helices is supported by weak sequential d(NN)(i, i + 1) NOEs. Thus, the m-domain consists of an N-terminal subdomain that is flexible and largely disordered and a C-terminal subdomain having a three-helix bundle fold, potentially providing an actin-binding platform.

PubMed: 22235120
DOI: 10.1074/jbc.M111.309591

Experimental method

SOLUTION NMR