Crystal structure of human otubain 2

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From Constructs to Crystals – Towards Structure Determination of β-barrel Outer Membrane Proteins
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Published on: July 4, 2016

Max H Nanao1, Sergey O Tcherniuk, Jadwiga Chroboczek

  • 1Laboratoire de Cristallographie Macromoléculaire, Institut de Biologie Structurale JP Ebel (CEA/CNRS/UJF), 41 rue Jules Horowitz, 38027 Grenoble, France.

EMBO Reports
|July 20, 2004
PubMed

Insights

Researchers reveal the novel structure of otubain 2, a deubiquitylating enzyme (DUB). This unique fold and active site explain otubain 2's specific substrate interactions and low activity in protein ubiquitylation regulation.

Area of Science:

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Ubiquitylation is a key post-translational modification regulating numerous cellular processes.
  • Deubiquitylating enzymes (DUBs) reverse ubiquitylation, controlling protein function.
  • Otubains, a family of DUBs within the OTU superfamily, play crucial roles in cellular regulation.

Purpose of the Study:

  • To determine the crystal structure of otubain 2, an OTU superfamily deubiquitylating enzyme.
  • To elucidate the structural basis for otubain 2's enzymatic activity and substrate specificity.

Main Methods:

  • X-ray crystallography was employed to determine the 2.1 Å resolution structure of otubain 2.
  • Comparative analysis with other DUB structures was performed to model otubain-ubiquitin binding.

Main Results:

  • The crystal structure reveals a novel fold for deubiquitylating enzymes within the ovarian tumour (OTU) superfamily.
  • Otubain 2 possesses a unique active-site cleft occlusion by a novel loop conformation.
  • The oxyanion hole is uniquely formed by backbone amides, and distinct residues stabilize the active-site histidine.

Conclusions:

  • The novel structural features of otubain 2, including its active-site topology, provide insights into its low turnover rate and substrate specificity.
  • This structural understanding is crucial for deciphering the regulatory mechanisms of ubiquitylation by otubain family DUBs.

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