PMID- 10411887
OWN - NLM
STAT- MEDLINE
DCOM- 19990823
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 15
DP  - 1999 Jul 20
TI  - A novel function for transglutaminase 1: attachment of long-chain
      omega-hydroxyceramides to involucrin by ester bond formation.
PG  - 8402-7
AB  - Transglutaminases (TGases) are defined as enzymes capable of forming isopeptide
      bonds by transfer of an amine onto glutaminyl residues of a protein. Here we show
      that the membrane-bound form of the TGase 1 enzyme can also form ester bonds
      between specific glutaminyl residues of human involucrin and a synthetic analog
      of epidermal specific omega-hydroxyceramides. The formation of a approximately
      5-nm-thick lipid envelope on the surface of epidermal keratinocytes is an
      important component of normal barrier function. The lipid envelope consists of
      omega-hydroxyceramides covalently linked by ester bonds to cornified envelope
      proteins, most abundantly to involucrin. We synthesized an analog of natural
      omega-hydroxyceramides N-[16-(16-hydroxyhexadecyl)oxypalmitoyl]sphingosine (lipid
      Z). When recombinant human TGase 1 and involucrin were reacted on the surface of 
      synthetic lipid vesicles containing lipid Z, lipid Z was attached to involucrin
      and formed saponifiable protein-lipid adducts. By mass spectroscopy and
      sequencing of tryptic lipopeptides, the ester linkage formation used involucrin
      glutamine residues 107, 118, 122, 133, and 496 by converting the
      gamma-carboxamido groups to lipid esters. Several of these residues have been
      found previously to be attached to ceramides in vivo. Mass spectrometric analysis
      after acetonide derivatization also revealed that ester formation involved
      primarily the omega-hydroxyl group of lipid Z. Our data reveal a dual role for
      TGase 1 in epidermal barrier formation and provide insights into the
      pathophysiology of lamellar ichthyosis resulting from defects of TGase 1 enzyme.
FAU - Nemes, Z
AU  - Nemes Z
AD  - Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal
      and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-2752, USA.
FAU - Marekov, L N
AU  - Marekov LN
FAU - Fesus, L
AU  - Fesus L
FAU - Steinert, P M
AU  - Steinert PM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Ceramides)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Peptide Fragments)
RN  - 0 (Protein Precursors)
RN  - 0 (Recombinant Proteins)
RN  - 0RH81L854J (Glutamine)
RN  - 60108-77-2 (involucrin)
RN  - EC 2.3.2.13 (Transglutaminases)
RN  - EC 2.3.2.13 (transglutaminase 1)
RN  - EC 3.4.21.4 (Trypsin)
RN  - V10TVZ52E4 (Putrescine)
SB  - IM
MH  - Amino Acid Sequence
MH  - Ceramides/*chemistry
MH  - Enzyme Inhibitors/pharmacology
MH  - Epidermis/metabolism
MH  - Esterification
MH  - Glutamine/metabolism
MH  - Humans
MH  - Ichthyosis/metabolism
MH  - Mass Spectrometry
MH  - Molecular Sequence Data
MH  - Molecular Structure
MH  - Peptide Fragments/analysis
MH  - Protein Precursors/*chemistry
MH  - Putrescine/pharmacology
MH  - Recombinant Proteins/metabolism
MH  - Sequence Analysis
MH  - Substrate Specificity
MH  - Transglutaminases/*metabolism
MH  - Trypsin
PMC - PMC17528
EDAT- 1999/07/21 00:00
MHDA- 1999/07/21 00:01
CRDT- 1999/07/21 00:00
PHST- 1999/07/21 00:00 [pubmed]
PHST- 1999/07/21 00:01 [medline]
PHST- 1999/07/21 00:00 [entrez]
AID - 10.1073/pnas.96.15.8402 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8402-7. doi:
      10.1073/pnas.96.15.8402.