Ester protein crosslinks

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Ester crosslinks between serine and the carboxy termini of proteases have been observed beginning in 2001 (see examples below). These are formed autocatalytically. Similar ester crosslinks exist in proteases in which ester intermediates in the catalytic process have been trapped (see examples below).

Ester bonds between threonine and glutamine sidechains can also form covalent crosslinks between polypeptide chains[1]. First observed in 2013 in repetitive domains of a putative surface-anchored adhesin of Clostridium perfringens (Gram positive)[1][2], analysis of sequences suggested "that these intramolecular ester bonds are a widespread and common feature of cell surface adhesion proteins in Gram-positive bacteria"[1]. In the examples studied, the Thr-Gln ester bonds occur between the first and last beta strands of immunoglobulin-like domains, increasing thermal stability and resisance to proteases[1]. The structures containing such ester crosslinks "have in common is that they are very long and thin but also subject to large mechanical shear stresses and protease-rich environments"[1].




  • 1gdq (2001): Ester catalytic intermediate trapped in trypsin.
  • 1jl0 (2001): Ester catalytic intermediate trapped in mutant decarboxylase.
  • 2pnl (2007): Protease VP4 of infectious pancreatic necrosis virus.
  • 3p06 (2011): Protease VP4 of tellina virus 1.
  • 4izk, 4izj (2013): Protease VP4 of yellowtail ascites virus.


  • 4ni6 (2013): Repeat domain 1 of Clostridium perfringens CPE0147 surface-anchored adhesin.
  • 4mkm (2013): Repeat domains 1 & 2 of Clostridium perfringens CPE0147 surface-anchored adhesin.

Detection and Visualization

FirstGlance in Jmol alerts you to protein crosslinks when present, and provides convenient links that zoom in and and display each one in detail. Viewing the electron density map is just one more click. Use the links above to 4-character PDB codes to go to a Proteopedia page titled with that 4-character PDB code. There, click on "FirstGlance". In FirstGlance, click on the Tools tab, and there, on "Protein Crosslinks". See the practical guide FirstGlance/Evaluating Protein Crosslinks.

Other Protein Crosslinks

In addition to the ester bonds discussed above, other covalent cross-links between polypeptide chains include:

See Also


  1. 1.0 1.1 1.2 1.3 1.4 Kwon H, Squire CJ, Young PG, Baker EN. Autocatalytically generated Thr-Gln ester bond cross-links stabilize the repetitive Ig-domain shaft of a bacterial cell surface adhesin. Proc Natl Acad Sci U S A. 2013 Dec 16. PMID:24344302 doi:
  2. Baker EN, Squire CJ, Young PG. Self-generated covalent cross-links in the cell-surface adhesins of Gram-positive bacteria. Biochem Soc Trans. 2015 Oct;43(5):787-94. doi: 10.1042/BST20150066. PMID:26517883 doi:

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