Consequences of seven novel mutations on the expression and structure of keratinocyte transglutaminase

Marcel Huber, Vivien C. Yee, Nathalie Burri, Eva Vikerfors, Adriana P.M. Lavrijsen, Amy S. Paller, Daniel Hohl*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


We report the molecular characterization of seven new keratinocyte transglutaminase mutations (R315C, S358R, V379L, G473S, R687C, deletion Δ679-696, R127Stop) found in lamellar ichthyosis patients. Arg-315, Ser- 358, Val-379, and Gly-473 are highly conserved residues in transglutaminases while Arg-687 and Δ679-696 are not. All mutations strongly decreased transglutaminase activity and protein levels. The mutation R127Stop diminished the amount of mRNA. Structural analysis of these mutations based on the factor XIII A-subunit crystal structure demonstrated that Arg-315, Ser-358, Val-379, and Gly-473 are located in the catalytic core domain, and Arg-687 and the deletion are in the β-barrel domains. The side chains of amino acids Arg-315, Ser-358, and Gly-473 make ionic and hydrogen bonds important for folding and structural stability of the enzyme but are not directly involved in catalysis. Val-379 is two amino acids away from the active site cysteine, and its change into leucine disturbs the active site structure. The decreased activity and protein level after expression of the R687C and Δ679-696 TGK cDNA in TGK negative keratinocytes excluded that they are polymorphisms. These results identify important amino acids in the central core domain of transglutaminases and show that the C-terminal end influences the structural and functional integrity of TGK.

Original languageEnglish (US)
Pages (from-to)21018-21026
Number of pages9
JournalJournal of Biological Chemistry
Issue number34
StatePublished - Aug 22 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Cell Biology


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