8-Cysteine TGF-BP structural motifs are the site of covalent binding between mouse LTBP-3, LTBP-2, and latent TGF-beta 1

Biochim Biophys Acta. 1998 Apr 2;1383(2):340-50. doi: 10.1016/s0167-4838(98)00003-x.


The small latent TGF-beta complex often is associated with the latent TGF-beta binding protein (LTBP). Three LTBPs (LTBP-1, -2, and -3) have been isolated to date. Previous studies have shown that LTBP-1 binds the small latent TGF-beta 1 complex through a disulfide bond between an 8-cysteine structural motif of LTBP-1 (TGF-bp repeat) and the propeptide dimer of latent TGF-beta 1 (TGF-beta 1 latency associated peptide). There is indirect evidence that LTBP-2 and LTBP-3 also bind the latent TGF-beta complex, but the nature and location of the binding interaction are unknown. We have used immunoprecipitation, SDS-PAGE, and autoradiography to characterize the association between mouse LTBP-3 and the small latent TGF-beta 1 complex. We report that the second and third TGF-bp repeats of LTBP-3 covalently bind the latent complex, and we show a similar capability for the homologous TGF-bp repeats of mouse LTBP-2. The second TGF-bp repeat of LTBP-3 is unusual in that it has 9 cysteine residues instead of 8, and our results provide the first evidence that a TGF-bp repeat with an odd number of cysteine residues can covalently bind latent TGF-beta 1. Altogether, these results have important implications for TGF-beta biosynthesis and the regulation of TGF-beta activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Cysteine / chemistry*
  • Latent TGF-beta Binding Proteins
  • Mice
  • Protein Binding
  • Transforming Growth Factor beta / chemistry*
  • Transforming Growth Factor beta / metabolism


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Latent TGF-beta Binding Proteins
  • Ltbp1 protein, mouse
  • Ltbp2 protein, mouse
  • Ltbp3 protein, mouse
  • Transforming Growth Factor beta
  • Cysteine