Oligomeric Aip2p/Dld2p modifies the protein conformation of both properly folded and misfolded substrates in vitro

Naomi S. Hachiya, Yuji Sakasegawa, Hiroyuki Sasaki, Akiko Jozuka, Shoichiro Tsukita, Kiyotoshi Kaneko

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Oligomeric actin-interacting protein 2 (Aip2p) [Nat. Struct. Biol. 2 (1995) 28]/d-lactate dehydrogenase protein 2 (Dld2p) [Yeast 15 (1999) 1377, Biochem. Biophys. Res. Commun. 295 (2002) 910] exhibits the unique grapple-like structure with an ATP-dependent opening [Biochem. Biophys. Res. Commun. 320 (2004) 1271], which is required for the F-actin conformation modifying activity in vitro and in vivo [Biochem. Biophys. Res. Commun. 319 (2004) 78]. To further investigate the molecular nature of oligomeric Aip2p/Dld2p, the substrate specificity of its binding and protein conformation modifying activity was examined. In the presence of 1 mM ATP or AMP-PNP, oligomeric Aip2p/Dld2p bound to all substrates so far examined, and modified the conformation of actin, DNase I, the mature form of invertase, prepro-α-factor, pro-α-factor, and mitochondrial superoxide dismutase, as determined by the trypsin susceptibility assay. Of note, the activity could modify even the conformation of pathogenic highly aggregated polypeptides, such as recombinant prion protein in β-sheet form, α-synuclein, and amyloid β (1-42) in the presence of ATP. The in vivo protein conformation modifying activity, however, depends on the growth stage; the most significant substrate modification activity was observed in yeast cells at the log phase, suggesting the presence of a cofactor/s in yeast cells, where F-actin is supposed to be a major target in vivo. These data further support our previous notion that the oligomeric Aip2p/Dld2p may belong to an unusual class of molecular chaperones [Biochem. Biophys. Res. Commun. 320 (2004) 1271], which can target both properly folded and misfolded proteins in an ATP-dependent manner in vitro.

Original languageEnglish
Pages (from-to)339-344
Number of pages6
JournalBiochemical and biophysical research communications
Volume323
Issue number1
DOIs
Publication statusPublished - 2004 Oct 8

Keywords

  • ATP-dependent conformation modifying activity
  • Actin interacting protein 2
  • Broad substrate specificity
  • Cell-cycle dependent
  • Oligomeric form
  • Trypsin susceptibility assay
  • d-Lactate dehydrogenase protein 2
  • β-Sheet conformation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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