SASDB25: Cardiac myosin binding protein-C: domains C5-C6-C7

Basic information

Entry

Database: SASBDB / ID: SASDB25

Sample

Cardiac myosin binding protein-C: domains C5-C6-C7

• Cardiac myosin binding protein-C: domains C5-C6-C7 (protein), cMyBP-C, Homo sapiens

Function / homology

Function:

C zone / regulation of muscle filament sliding / striated muscle myosin thick filament / A band / regulation of striated muscle contraction / cardiac myofibril / Striated Muscle Contraction / M band / regulation of cardiac muscle cell contraction / structural constituent of muscle / sarcomere organization / myosin heavy chain binding / ventricular cardiac muscle tissue morphogenesis / myosin binding / ATPase activator activity / heart morphogenesis / cardiac muscle contraction / titin binding / sarcomere / actin binding / cell adhesion / metal ion binding / identical protein binding / cytosol

Domain/homology:

: / MyBP-C, tri-helix bundle domain / Tri-helix bundle domain / Immunoglobulin I-set / Immunoglobulin I-set domain / Fibronectin type III domain / Fibronectin type 3 domain / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold

Component:

Myosin-binding protein C, cardiac-type

• Biological species: Homo sapiens (human)
• Citation: Journal: Structure / Year: 2016; Title: Clinically Linked Mutations in the Central Domains of Cardiac Myosin-Binding Protein C with Distinct Phenotypes Show Differential Structural Effects.; Authors: Naveed Ahmed Nadvi / Katharine A Michie / Ann H Kwan / J Mitchell Guss / Jill Trewhella / ; Abstract: The structural effects of three missense mutations clinically linked to hypertrophic cardiomyopathy (HCM) and located in the central domains of cardiac myosin-binding protein C (cMyBP-C) have been determined using small-angle scattering, infrared spectroscopy, and nuclear magnetic resonance spectroscopy. Bioinformatics and modeling were used to initially predict the expected structural impacts and assess the broader implications for function based on sequence conservation patterns. The experimental results generally affirm the predictions that two of the mutations (D745G, P873H) disrupt domain folding, while the third (R820Q) is likely to be entirely solvent exposed and thus more likely to have its impact through its interactions within the sarcomere. Each of the mutations is associated with distinct disease phenotypes, with respect to severity, stage of onset, and end phase. The results are discussed in terms of understanding key structural features of these domains essential for healthy function and the role they may play in disease development.

Contact author

• Jill Trewhella (School of Molecular Bioscience, University of Sydney., Sydney, New South Wales 2006, Australia)

Models

Sample

• Sample: Name: Cardiac myosin binding protein-C: domains C5-C6-C7 / Specimen concentration: 0.70-3.40
• Buffer: Name: 25 mM Tris-HCl, 250 mM NaCl, 2 mM TCEP, 0.02% sodium azide; Concentration: 25.00 mM / pH: 7.5 / Composition: 250 mM NaCl, 2 mM TCEP, 0.02% sodium azide

Entity #352

Name: cMyBP-C / Type: protein
Description: Cardiac myosin binding protein-C: domains C5-C6-C7
Formula weight: 35.751 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: Q14896
Sequence:

GPGSRQEPPK IHLDCPGRIP DTIVVVAGNK LRLDVPISGD PAPTVIWQKA ITQGNKAPAR PAPDAPEDTG DSDEWVFDKK LLCETEGRVR VETTKDRSIF TVEGAEKEDE GVYTVTVKNP VGEDQVNLTV KVIDVPDAPA APKISNVGED SCTVQWEPPA YDGGQPILGY ILERKKKKSY RWMRLNFDLI QELSHEARRM IEGVVYEMRV YAVNAIGMSR PSPASQPFMP IGPPSEPTHL AVEDVSDTTV SLKWRPPERV GAGGLDGYSV EYCPEGCSEW VAALQGLTEH TSILVKDLPT GARLLFRVRA HNMAGPGAPV TTTEPVTV

Experimental information

• Beam: Instrument name: Australian Synchrotron SAXS/WAXS / City: Melbourne / 国: Australia / Shape: Point / Type of source: X-ray synchrotron / Dist. spec. to detc.: 1.6 mm
• Detector: Name: Pilatus 1M

Scan

Title: cMyBP-C; domains C5-C6-C7 / Measurement date: Apr 18, 2015 / Storage temperature: 22 °C / Cell temperature: 22 °C / Exposure time: 1 sec. / Number of frames: 44 / Unit: 1/nm /

	Min	Max
Q	0.0566	3.436

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 728 /

	Min	Max
Q	0.142443	2.97692
P(R) point	1	728
R	0	14.1

Result

Type of curve: extrapolated /

	Experimental	Porod
MW	38.2 kDa	-
Volume	-	54.7 nm3

	P(R)	Guinier	Guinier error	P(R) error
Forward scattering, I0	0.1068	0.1055	0.0001	-
Radius of gyration, Rg	3.931 nm	3.75 nm	0.01	0.001

	Min	Max
D	-	14.1
Guinier point	15	75