Structural Basis for the Persistence of Homing Endonucleases in Transcription Factor IIB Inteins

J Mol Biol. 2017 Dec 8;429(24):3942-3956. doi: 10.1016/j.jmb.2017.10.016. Epub 2017 Oct 18.

Abstract

Inteins are mobile genetic elements that are spliced out of proteins after translation. Some inteins contain a homing endonuclease (HEN) responsible for their propagation. Hedgehog/INTein (HINT) domains catalyzing protein splicing and their nested HEN domains are thought to be functionally independent because of the existence of functional mini-inteins without HEN domains. Despite the lack of obvious mutualism between HEN and HINT domains, HEN domains are persistently found at one specific site in inteins, indicating their potential functional role in protein splicing. Here we report crystal structures of inactive and active mini-inteins derived from inteins residing in the transcription factor IIB of Methanococcus jannaschii and Methanocaldococcus vulcanius, revealing a novel modified HINT fold that might provide new insights into the mutualism between the HEN and HINT domains. We propose an evolutionary model of inteins and a functional role of HEN domains in inteins.

Keywords: homing endonuclease; horizontal gene transfer; inteins; protein splicing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Endonucleases / chemistry*
  • Endonucleases / genetics
  • Endonucleases / metabolism
  • Inteins*
  • Methanococcus / enzymology*
  • Methanococcus / genetics
  • Models, Molecular
  • Protein Conformation
  • Protein Splicing
  • Sequence Homology
  • Transcription Factor TFIIB / chemistry*
  • Transcription Factor TFIIB / genetics
  • Transcription Factor TFIIB / metabolism

Substances

  • Transcription Factor TFIIB
  • Endonucleases