Substrate Preference of Transglutaminase 2 Revealed by Logistic Regression Analysis and Intrinsic Disorder Examination

Eva Csosz, P. Bagossi, Zoltan Nagy, Z. Dosztányi, I. Simon, L. Fésüs

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Tissue transglutaminase (TG2) catalyzes the Ca2+-dependent posttranslational modification of proteins via formation of isopeptide bonds between their glutamine and lysine residues. Although substrate specificity of TG2 has been studied repeatedly at the sequence level, no clear consensus sequences have been determined so far. With the use of the extensive structural information on TG2 substrate proteins listed in TRANSDAB Wiki database††http://genomics.dote.hu/wiki, a slight preference of TG2 for glutamine and lysine residues situated in turns could be observed. When the spatial environment of the favored glutamine and lysine residues was analyzed with logistic regression, the presence of specific amino acid patterns was identified. By using the occurrence of the predictor amino acids as selection criteria, several polypeptides were predicted and later identified as novel in vitro substrates for TG2. By studying the sequence of TG2 substrate proteins lacking available crystal structure, the strong favorable influence on substrate selection of the presence of substrate glutamine and lysine residues in intrinsically disordered regions could also be revealed. The collected structural data have provided novel understanding of how this versatile enzyme selects its substrates in various cell compartments and tissues.

Original languageEnglish
Pages (from-to)390-402
Number of pages13
JournalJournal of Molecular Biology
Volume383
Issue number2
DOIs
Publication statusPublished - Nov 7 2008

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Glutamine
Lysine
Logistic Models
Regression Analysis
Amino Acids
Proteins
Consensus Sequence
Post Translational Protein Processing
Substrate Specificity
Genomics
Patient Selection
Peptides
transglutaminase 2
Enzymes

Keywords

  • 3D structure
  • glutamine and lysine site
  • IUP
  • substrate preference
  • TG2

ASJC Scopus subject areas

  • Molecular Biology

Cite this

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abstract = "Tissue transglutaminase (TG2) catalyzes the Ca2+-dependent posttranslational modification of proteins via formation of isopeptide bonds between their glutamine and lysine residues. Although substrate specificity of TG2 has been studied repeatedly at the sequence level, no clear consensus sequences have been determined so far. With the use of the extensive structural information on TG2 substrate proteins listed in TRANSDAB Wiki database††http://genomics.dote.hu/wiki, a slight preference of TG2 for glutamine and lysine residues situated in turns could be observed. When the spatial environment of the favored glutamine and lysine residues was analyzed with logistic regression, the presence of specific amino acid patterns was identified. By using the occurrence of the predictor amino acids as selection criteria, several polypeptides were predicted and later identified as novel in vitro substrates for TG2. By studying the sequence of TG2 substrate proteins lacking available crystal structure, the strong favorable influence on substrate selection of the presence of substrate glutamine and lysine residues in intrinsically disordered regions could also be revealed. The collected structural data have provided novel understanding of how this versatile enzyme selects its substrates in various cell compartments and tissues.",
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AU - Bagossi, P.

AU - Nagy, Zoltan

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AU - Simon, I.

AU - Fésüs, L.

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AB - Tissue transglutaminase (TG2) catalyzes the Ca2+-dependent posttranslational modification of proteins via formation of isopeptide bonds between their glutamine and lysine residues. Although substrate specificity of TG2 has been studied repeatedly at the sequence level, no clear consensus sequences have been determined so far. With the use of the extensive structural information on TG2 substrate proteins listed in TRANSDAB Wiki database††http://genomics.dote.hu/wiki, a slight preference of TG2 for glutamine and lysine residues situated in turns could be observed. When the spatial environment of the favored glutamine and lysine residues was analyzed with logistic regression, the presence of specific amino acid patterns was identified. By using the occurrence of the predictor amino acids as selection criteria, several polypeptides were predicted and later identified as novel in vitro substrates for TG2. By studying the sequence of TG2 substrate proteins lacking available crystal structure, the strong favorable influence on substrate selection of the presence of substrate glutamine and lysine residues in intrinsically disordered regions could also be revealed. The collected structural data have provided novel understanding of how this versatile enzyme selects its substrates in various cell compartments and tissues.

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