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J Biol Chem, Vol. 274, Issue 11, 7226-7237, March 12, 1999
Transglutaminase Cross-linking Properties of the Small
Proline-rich 1 Family of Cornified Cell Envelope Proteins
INTEGRATION WITH LORICRIN
Eleonora
Candi,
Edit
Tarcsa,
William W.
Idler,
Tonja
Kartasova,
Lyuben N.
Marekov, and
Peter M.
Steinert
From the Laboratory of Skin Biology, NIAMS, National Institutes of
Health, Bethesda, Maryland 20892-2752
Small proline-rich 1 (SPR1) proteins are
important for barrier function in stratified squamous epithelia. To
explore their properties, we expressed in bacteria a recombinant human
SPR1 protein and isolated native SPR1 proteins from cultured mouse keratinocytes. By circular dichroism, they possess no or structure but have some organized structure associated with their
central peptide repeat domain. The transglutaminase (TGase) 1 and 3 enzymes use the SPR1 proteins as complete substrates in
vitro but in different ways: head domain A sequences at the amino
terminus were used preferentially for cross-linking by TGase 3, whereas
those in head domain B sequences were used for cross-linking by TGase
1. The TGase 2 enzyme cross-linked SPR1 proteins poorly. Together with
our data base of 141 examples of in vivo cross-links
between SPRs and loricrin, this means that both TGase 1 and 3 are
required for cross-linking SPR1 proteins in epithelia in
vivo. Double in vitro cross-linking experiments
suggest that oligomerization of SPR1 into large polymers can occur only
by further TGase 1 cross-linking of an initial TGase 3 reaction.
Accordingly, we propose that TGase 3 first cross-links loricrin and
SPRs together to form small interchain oligomers, which are then
permanently affixed to the developing CE by further cross-linking by
the TGase 1 enzyme. This is consistent with the known consequences of
diminished barrier function in TGase 1 deficiency models.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
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