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Structure and function of the N-terminal region of cardiac Myosin binding protein - C

Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.14/26581

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Title: Structure and function of the N-terminal region of cardiac Myosin binding protein - C
Related: Annual Meeting of the Biophysical Society (50th : 2006) (18 - 22 February 2006 : Salt Lake City, Utah)
Related: Callender, Robert. Biophysical Society Meeting Abstracts. Biophysical Journal. Supplement, Vol. 90,
Related: http://www.abstractsonline.com/viewer/viewAbstractPrintFriendly.asp?CKey={79AFE9DD-856B-427F-B7CF-38B1EE9A7971}&SKey={E299667C-A6F8-4D01-95E5-9D2FDCFA1BC1}&MKey={BDF19C6B-CD15-4FA3-A327-820BB93F0A13}&AKey={E8823E6D-A533-47A9-8D69-CD2B15557315}
Publisher: Bethseda, MD : Biophysical Society
Date: 2006
FoR/RFCD Code(s): 249901 Biophysics
Author/Creator: Oakley, Cecily E
Author/Creator: Brown, Louise J
Author/Creator: Kekic, Murat
Author/Creator: Fajer, Piotr G
Author/Creator: Hambly, Brett D
Description: Myosin binding protein - C (MyBPC) is a multi-domain protein whose role in the sarcomere is complex and not yet fully understood. The cardiac isoform is linked to familial hypertrophic cardiomyopathy (FHC), which is caused by the expression of abnormal sarcomeric proteins, including numerous mutations in MyBPC. The core structure of cardiac MyBPC consists of eight immunoglobulin (IgI) and three fibronectin (FnIII) domains, numbered 0 - 10 from the N-terminus. The C-terminus of MyBPC binds to titin and the myosin backbone and may bind other MyBPC molecules. At its N-terminus, MyBPC binds myosin S2 when dephosphorylated and may bind the myosin head and actin. MyBPC is phosphorylated up to 3 times in the linker between IgI domains 1 and 2, causing dissociation from S2 and increased contractile force. The role of partial phosphorylation remains unclear. The N-terminal construct, C1C2 (two IgI domains linked by the phosphorylatable linker), has been cloned, expressed, and purified. FHC and permanently phosphorylated mutants have also been produced. The constructs were studied by modelling, circular dichroic (CD) spectroscopy and myosin binding assays. Modelling of the C1C2 construct suggests an alpha-helical content within the phosphorylation linker region. CD spectra confirmed that a fraction of the protein is indeed alpha-helix. CD spectral changes for several FHC mutants indicate secondary structural change. C1C2 binding to myosin was confirmed using a sedimentation assay. Surprisingly, C1C2 also binds to actin, but only in its filamentous form, and this binding appears to be phosphorylation dependent.
Subject Keyword: 249901 Biophysics
Subject Keyword: muscle regulatory proteins
Resource Type: conference paper abstract
Organisation: Macquarie University. Dept. of Chemistry and Biomolecular Sciences

Identifier: http://hdl.handle.net/1959.14/26581
Identifier: ISSN:1542-0086
Identifier: mq-rm-2006000469
Language: eng

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