What question did this study set out to answer?

Identify specific conserved amino acid residues in the C-terminal extracellular matrix (ECM) binding domain of rat IGFBP-5 that govern binding affinity for IGF-I.

August 1, 1999Journal of Molecular EndocrinologyOpen Access

Amino acids within the extracellular matrix (ECM) binding region (201-218) of rat insulin-like growth factor binding protein (IGFBP)-5 are important determinants in binding IGF-I

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Population

Recombinant rat insulin-like growth factor binding protein (IGFBP)-5

Comparison

Site-directed mutagenesis producing G203K and… vs Wild-type rIGFBP-5

Design

Preclinical

Authors

SBSilvia BramaniUniversity of Milan HSHyuk SongKonkuk University JBJames BeattieHeart Failure & Transplant

Discussion

Member takes

Implication

These affinity reductions in rat IGFBP-5 mutants do not inform clinical practice; leaves open whether C-terminal overlap enables targeted IGF-I modulation in vivo.

Key Points

Identify specific conserved amino acid residues in the C-terminal extracellular matrix (ECM) binding domain of rat IGFBP-5 that govern binding affinity for IGF-I.
Generated rat IGFBP-5 mutants G203K and Q209A using site-directed mutagenesis.
Evaluated binding affinity of recombinant wild-type and mutant proteins to human IGF-I using IGF-I ligand blots and solution-phase ligand binding assays.
The G203K mutant demonstrated an 8-fold reduction in binding affinity for human IGF-I in both ligand blot and solution-phase binding assays relative to wild-type rIGFBP-5.
The Q209A mutant showed a 7-fold reduction in affinity in ligand blots and a 6-fold reduction in solution-phase assays.
Residues Gly203 and Gln209 localize within the 201–218 ECM-binding domain, indicating that extracellular matrix attachment physically overlaps with and occludes the IGF-I binding interface.

Structured PICO

Population

Recombinant rat insulin-like growth factor binding protein (IGFBP)-5

Intervention

Site-directed mutagenesis producing G203K and Q209A mutants

Comparator

Wild-type rIGFBP-5

Outcome

Affinity for human IGF-I measured by IGF-I ligand blots and solution phase ligand binding assayssurrogate

Gly203 and Gln209 in IGFBP-5 are important determinants in binding IGF-I, demonstrating that the C-terminus contains partially overlapping IGF-I and ECM binding sites.

Cite This Study

Bramani et al. (1999) studied this question.

synapsesocial.com/papers/6a7fa03a3684647f4818f247 https://doi.org/10.1677/jme.0.0230117

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Implication

These affinity reductions in rat IGFBP-5 mutants do not inform clinical practice; leaves open whether C-terminal overlap enables targeted IGF-I modulation in vivo.

Amino acids within the extracellular matrix (ECM) binding region (201-218) of rat insulin-like growth factor binding protein (IGFBP)-5 are important determinants in binding IGF-I

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Amino acids within the extracellular matrix (ECM) binding region (201-218) of rat insulin-like growth factor binding protein (IGFBP)-5 are important determinants in binding IGF-I

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider