Apr 14, 2020

Molecular basis for the recognition of steroidogenic acute regulatory protein by the 14-3-3 protein family

BioRxiv : the Preprint Server for Biology
K. V. TugaevaNikolai N. Sluchanko


Steroidogenesis in adrenals and gonads starts from cholesterol transport to mitochondria by the steroidogenic acute regulatory protein STARD1, containing a mitochondrial import sequence followed by a cholesterol-binding START domain. Although mutations in this protein have been linked to lipoid congenital adrenal hyperplasia, the mechanism of steroidogenesis regulation by the STARD1 remains debatable, hypothetically involving a molten-globule structural transition and interaction with 14-3-3 proteins. We show that, while the isolated START domain does not interact with 14-3-3, interaction is enabled by STARD1 phosphorylation at Ser57, close to the mitochondrial peptide cleavage site. Biochemical analysis of the STARD1 affinity towards 14-3-3 and crystal structures of 14-3-3 complexes with Ser57 and Ser195 phosphopeptides, suggest distinct roles of site-specific phosphorylations in recruiting 14-3-3, to modulate STARD1 activity, processing and import to mitochondria. Phosphorylation at Ser195 creates a unique conditional site, that could only bind to 14-3-3 upon partial unfolding of the START domain.

  • References
  • Citations


  • We're still populating references for this paper, please check back later.
  • References
  • Citations


  • This paper may not have been cited yet.

Mentioned in this Paper

Biological Markers
Gene Polymorphism
DNA Groove Binding
The Cancer Genome Atlas
Tumor Tissue Sample
HLA-DQB1 gene
HLA-DQB1 wt Allele
Adenocarcinoma of Colon

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.