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@ARTICLE{Dall:878252,
      author       = {Dall, Elfriede and Zauner, Florian B and Soh, Wai Tuck and
                      Demir, Fatih and Dahms, Sven O. and Cabrele, Chiara and
                      Huesgen, Pitter F. and Brandstetter, Hans},
      title        = {{S}tructural and functional studies of {A}rabidopsis
                      thaliana legumain beta reveal isoform specific mechanisms of
                      activation and substrate recognition},
      journal      = {The journal of biological chemistry},
      volume       = {295},
      issn         = {1083-351X},
      address      = {Bethesda, Md.},
      publisher    = {Soc.72889},
      reportid     = {FZJ-2020-02721},
      pages        = {13047-13064},
      year         = {2020},
      abstract     = {The vacuolar cysteine protease legumain plays important
                      functions in seed maturation and plant programmed cell
                      death. Because of their dual protease and ligase activity,
                      plant legumains have become of particular biotechnological
                      interest, e.g. for the synthesis of cyclic peptides for drug
                      design or for protein engineering. However, the molecular
                      mechanisms behind their dual protease and ligase activities
                      are still poorly understood, limiting their applications.
                      Here, we present the crystal structure of Arabidopsis
                      thaliana legumain isoform β (AtLEGβ) in its zymogen state.
                      Combining structural and biochemical experiments, we show
                      for the first time that plant legumains encode distinct,
                      isoform-specific activation mechanisms. Whereas the
                      autocatalytic activation of isoform γ (AtLEGγ) is
                      controlled by the latency-conferring dimer state, the
                      activation of the monomeric AtLEGβ is concentration
                      independent. Additionally, in AtLEGβ the
                      plant-characteristic two-chain intermediate state is
                      stabilized by hydrophobic rather than ionic interactions, as
                      in AtLEGγ, resulting in significantly different pH
                      stability profiles. The crystal structure of AtLEGβ
                      revealed unrestricted nonprime substrate binding pockets,
                      consistent with the broad substrate specificity, as
                      determined by degradomic assays. Further to its protease
                      activity, we show that AtLEGβ exhibits a true peptide
                      ligase activity. Whereas cleavage-dependent transpeptidase
                      activity has been reported for other plant legumains,
                      AtLEGβ is the first example of a plant legumain capable of
                      linking free termini. The discovery of these
                      isoform-specific differences will allow us to identify and
                      rationally design efficient ligases with application in
                      biotechnology and drug development.},
      cin          = {ZEA-3},
      ddc          = {540},
      cid          = {I:(DE-Juel1)ZEA-3-20090406},
      pnm          = {582 - Plant Science (POF3-582) / ProPlantStress -
                      Proteolytic processing in plant stress signal transduction
                      and responses to abiotic stress and pathogen attack
                      (639905)},
      pid          = {G:(DE-HGF)POF3-582 / G:(EU-Grant)639905},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32719006},
      UT           = {WOS:000572412900015},
      doi          = {10.1074/jbc.RA120.014478},
      url          = {https://juser.fz-juelich.de/record/878252},
}