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Updated: Jul 12, 2026

Characterization of Glycoproteins with the Immunoglobulin Fold by X-Ray Crystallography and Biophysical Techniques
Published on: July 5, 2018
Structure-function relationships of insulin-like growth factor binding protein 6 (IGFBP-6) and its chimeras
1Department of Internal Medicine, Veterans Administration Medical Center, Iowa City, IA 52246, USA.
Abstract:
Insulin-like growth factor binding protein 6 (IGFBP-6) is a high-affinity IGFBP with substantially greater affinity for insulin-like growth factor-II (IGF-II) than IGF-I. IGFBP-6(3) is a chimera which has a 20 amino acidC -terminal portion of IGFBP-6 switched with the homologous area of IGFBP-3, P3. Unlike IGFBP-4(3), in which the P3 region was exchanged for the homologous region of IGFBP-4 (P4), IGFBP-6(3) does not bind to endothelial cells. Double mutations were made with the P3 region exchanged as well as a second area differing from IGFBP-3 to form IGFBP-6(3)A and IGFBP-6(3)B, by replacing this area with the homologous region of IGFBP-3. Neither [(125)I]IGFBP-6(3)A nor IGFBP-6(3)B specifically bound to endothelial cells. However, each double mutant competed for [(125)I]IGFBP-3 binding to cultured cells. In the perfused heart, transendothelial transport of IGFBP-6 and IGFBP-6(3) was only 25% of similar transendothelial transport of perfused IGFBP-3. We conclude that chimeras of IGFBP-6 and IGFBP-3(6) clearly differ from IGFBP-4(3) in their ability to bind specifically to endothelial cells and in their capacity to undergo transendothelial transportation in the perfused heart.
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