Binding of smoothelin-like 1 to tropomyosin and calmodulin is mutually exclusive and regulated by phosphorylation

BMC Biochem. 2017 Mar 21;18(1):5. doi: 10.1186/s12858-017-0080-6.

Abstract

Background: The smoothelin-like 1 protein (SMTNL1) can associate with tropomyosin (Tpm) and calmodulin (CaM), two proteins essential to the smooth muscle contractile process. SMTNL1 is phosphorylated at Ser301 by protein kinase A during calcium desensitization in smooth muscle, yet the effect of SMTNL1 phosphorylation on Tpm- and CaM-binding has yet to be investigated.

Results: Using pull down studies with Tpm-Sepharose and CaM-Sepharose, we examined the interplay between Tpm binding, CaM binding, phosphorylation of SMTNL1 and calcium concentration. Phosphorylation greatly enhanced the ability of SMTNL1 to associate with Tpm in vitro; surface plasmon resonance yielded a 10-fold enhancement in K D value with phosphorylation. The effect on CaM binding is more complex and varies with the availability of calcium.

Conclusions: Combining both CaM and Tpm with SMTNL1 shows that the binding to both is mutually exclusive.

Keywords: CHASM; Protein binding; SMTNL1; Smooth muscle; Thin filament.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calmodulin / metabolism*
  • Chickens
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Muscle Proteins / chemistry
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Muscle, Smooth / metabolism
  • Phosphorylation
  • Protein Binding
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Tropomyosin / metabolism*

Substances

  • Calmodulin
  • Muscle Proteins
  • Recombinant Proteins
  • Tropomyosin
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium

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