Myopathy-causing mutation R91P in the TPM3 gene drastically impairs structural and functional properties of slow skeletal muscle tropomyosin γß-heterodimer.
Arch Biochem Biophys
; 752: 109881, 2024 02.
Article
in En
| MEDLINE
| ID: mdl-38185233
ABSTRACT
Tropomyosin (Tpm) is a regulatory actin-binding protein involved in Ca2+ activation of contraction of striated muscle. In human slow skeletal muscles, two distinct Tpm isoforms, γ and ß, are present. They interact to form three types of dimeric Tpm molecules γγ-homodimers, γß-heterodimers, or ßß-homodimers, and a majority of the molecules are present as γß-Tpm heterodimers. Point mutation R91P within the TPM3 gene encoding γ-Tpm is linked to the condition known as congenital fiber-type disproportion (CFTD), which is characterized by severe muscle weakness. Here, we investigated the influence of the R91P mutation in the γ-chain on the properties of the γß-Tpm heterodimer. We found that the R91P mutation impairs the functional properties of γß-Tpm heterodimer more severely than those of earlier studied γγ-Tpm homodimer carrying this mutation in both γ-chains. Since a significant part of Tpm molecules in slow skeletal muscle is present as γß-heterodimers, our results explain why this mutation leads to muscle weakness in CFTD.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tropomyosin
/
Muscular Diseases
Limits:
Humans
Language:
En
Journal:
Arch Biochem Biophys
Year:
2024
Document type:
Article
Affiliation country:
Rusia
Country of publication:
Estados Unidos