Localization of the binding interface between leiomodin-2 and α-tropomyosin

Mert Colpan; Dmitri Tolkatchev; Samantha Grover; Gregory L Helms; John R Cort; Natalia Moroz; Alla S Kostyukova

doi:10.1016/j.bbapap.2016.02.009

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Localization of the binding interface between leiomodin-2 and α-tropomyosin

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Localization of the binding interface between leiomodin-2 and α-tropomyosin

Mert Colpan, Dmitri Tolkatchev, Samantha Grover, Gregory L Helms, John R Cort, Natalia Moroz and Alla S Kostyukova

Biochimica et biophysica acta. Proteins and proteomics, Vol.1864(5), pp.523-530

05/2016

DOI: https://doi.org/10.1016/j.bbapap.2016.02.009

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https://hdl.handle.net/2376/116896

PMCID: PMC5079754

PMID: 26873245

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https://doi.org/10.1016/j.bbapap.2016.02.009View

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Abstract

Tropomodulin

Leiomodin

Nuclear magnetic resonance

Dilated cardiomyopathy

Intrinsically disordered regions

Circular dichroism

The development of some familial dilated cardiomyopathies (DCM) correlates with the presence of mutations in proteins that regulate the organization and function of thin filaments in cardiac muscle cells. Harmful effects of some mutations might be caused by disruption of yet uncharacterized protein–protein interactions. We used nuclear magnetic resonance spectroscopy to localize the region of striated muscle α-tropomyosin (Tpm1.1) that interacts with leiomodin-2 (Lmod2), a member of tropomodulin (Tmod) family of actin-binding proteins. We found that 21 N-terminal residues of Tpm1.1 are involved in interactions with residues 7–41 of Lmod2. The K15N mutation in Tpm1.1, known to be associated with familial DCM, is located within the newly identified Lmod2 binding site of Tpm1.1. We studied the effect of this mutation on binding Lmod2 and Tmod1. The mutation reduced binding affinity for both Lmod2 and Tmod1, which are responsible for correct lengths of thin filaments. The effect of the K15N mutation on Tpm1.1 binding to Lmod2 and Tmod1 provides a molecular rationale for the development of familial DCM. •21 N-terminal residues of tropomyosin (Tpm1.1) represent leiomodin-2 binding site.•Dilated cardiomyopathy-causing mutation K15N disrupts the structure of Tpm1.1.•K15N mutation decreases Tpm1.1 binding to leiomodin-2 and tropomodulin-1.

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Title: Localization of the binding interface between leiomodin-2 and α-tropomyosin
Creators: Mert Colpan - Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA 99164-6515, USA
Dmitri Tolkatchev - Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA 99164-6515, USA
Samantha Grover - Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA 99164-6515, USA
Gregory L Helms - The Center for NMR Spectroscopy, Washington State University, Pullman, WA 99164-4630, USA
John R Cort - Fundamental & Computational Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA 99354, USA
Natalia Moroz - Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA 99164-6515, USA
Alla S Kostyukova - Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA 99164-6515, USA
Publication Details: Biochimica et biophysica acta. Proteins and proteomics, Vol.1864(5), pp.523-530
Academic Unit: Plant Pathology, Department of; NMR Center; Chemical Engineering and Bioengineering, School of
Publisher: Elsevier B.V
Identifiers: 99900547661201842
Language: English
Resource Type: Journal article