Calmodulin binds to the STAS domain of SLC26A5 prestin with a calcium-dependent, one-lobe, binding mode.
J Struct Biol
; 213(2): 107714, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33667636
ABSTRACT
SLC26A5 transporter prestin is fundamental for the higher hearing sensitivity and frequency selectivity of mammals. Prestin is a voltage-dependent transporter found in the cochlear outer hair cells responsible for their electromotility. Intracellular chloride binding is considered essential for voltage sensitivity and electromotility. Prestin is composed by a transmembrane domain and by a cytosolic domain called STAS. There is evidence of a calcium/calmodulin regulation of prestin mediated by the STAS domain. Using different biophysical techniques, namely SEC, CD, ITC, MST, NMR and SAXS, here we demonstrate and characterize the direct interaction between calmodulin and prestin STAS. We show that the interaction is calcium-dependent and that involves residues at the N-terminal end of the "variable loop". This is an intrinsically disordered insertion typical of the STAS domains of the SLC26 family of transporters whose function is still unclear. We derive a low-resolution model of the STAS/CaM complex, where only one lobe of calmodulin is engaged in the interaction, and build a model for the entire dimeric prestin in complex with CaM, which can use the unoccupied lobe to interact with other regions of prestin or with other regulatory proteins. We show that also a non-mammalian STAS can interact with calmodulin via the variable loop. These data start to shed light on the regulatory role of the STAS variable loop of prestin.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Calmodulina
/
Transportadores de Sulfato
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Struct Biol
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Itália