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The third Trp-Lys-Ser (WKS) tripeptide motif in tissue factor is associated with a function site

Academic Article
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Overview

authors

  • Rehemtulla, A.
  • Ruf, Wolfram
  • Miles, D. J.
  • Edgington, Thomas

publication date

  • 1992

journal

  • Biochemical Journal  Journal

abstract

  • The tripeptide sequence Trp-Lys-Ser (WKS) is repeated three times in the extracellular ligand binding domain of human Tissue Factor (TF). Using site-directed mutagenesis, we replaced each of the WKS motifs in human TF by Arg-Lys-Gly (RKG), the least conserved replacement for the motif found in murine TF. This substitution in the first repeat W14KS, as well as a Trp14----Arg substitution, resulted in a structurally altered protein, whereas a conservative hydrophobic Trp14----Phe substitution resulted in a functionally normal protein. This suggests that Trp14 may contribute to a hydrophobic core rather than involvement of this motif in function. Replacement of the W45KS and W158KS motifs was associated with no detectable structural alterations; however, function was diminished with the RKG replacement of the third repeat. Mutant proteins with Lys159----Ala and Tyr157----Ala substitutions exhibited loss of function, whereas Tyr156----Ala and Ser160----Ala substitutions flanking the YWK sequence resulted in functional proteins. These data demonstrate that the W158KS motif in human TF is associated with a functional site and identify Lys159 in this motif as a functionally important residue.

subject areas

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Exons
  • Extracellular Space
  • Humans
  • Mice
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Conformation
  • Rabbits
  • Repetitive Sequences, Nucleic Acid
  • Sequence Homology, Nucleic Acid
  • Thromboplastin
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Identity

PubMed Central ID

  • PMC1130849

International Standard Serial Number (ISSN)

  • 0264-6021

PubMed ID

  • 1554354
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Additional Document Info

start page

  • 737

end page

  • 740

volume

  • 282

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