Localization of the binding interface between leiomodin-2 and alpha-tropomyosin.
Article Details
- CitationCopy to clipboard
Colpan M, Tolkatchev D, Grover S, Helms GL, Cort JR, Moroz N, Kostyukova AS
Localization of the binding interface between leiomodin-2 and alpha-tropomyosin.
Biochim Biophys Acta. 2016 May;1864(5):523-30. doi: 10.1016/j.bbapap.2016.02.009. Epub 2016 Feb 9.
- PubMed ID
- 26873245 [ View in PubMed]
- Abstract
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 alpha-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.