2LHU

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

2LHU の概要

• エントリーDOI: 10.2210/pdb2lhu/pdb
• NMR情報: BMRB: 17867
• 分子名称: Mybpc3 protein (1 entity in total)
• 機能のキーワード: cardiac, structural protein
• 由来する生物種: Mus musculus (mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13997.66

構造登録者

Howarth, J.W.,Rosevear, P.R.,Ramisetti, S.,Nolan, K.,Sadayappan, S. (登録日: 2011-08-18, 公開日: 2012-01-11, 最終更新日: 2024-05-01)

主引用文献

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

実験手法

SOLUTION NMR