Solution Structure and Backbone Dynamics of Long-[Arg3]insulin-like Growth Factor-I

Laajoki, Leanne G; Francis, G L; Wallace, John C.; Carver, John A.; Keniry, Max A.

doi:10.1074/jbc.275.14.10009

Cited by 24 publications

(35 citation statements)

References 33 publications

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“…Similarly, the general fold of free IGF-I reported in NMR solution studies [19][20][21] was preserved in the crystal complex [17]. Although the structures were highly defined for most residues, less definition in the crystal structure of IGF-I was seen for residues 1-6, 31-40 (which form a solvent exposed loop) and 62-67 [17], which is consistent with NMR data in those regions [19][20][21].…”

Section: Structural Evidence For Igfbp Residues Involved In the Igfbpsupporting

confidence: 85%

The interaction of Insulin-like Growth Factors (IGFs) with Insulin-like Growth Factor Binding Proteins (IGFBPs): a review

2001

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SummaryThe interactions between insulin-like growth factor binding proteins (IGFBPs) and insulin-like growth factors (IGFs) are important in regulating the availability of IGFs to the type 1 IGF receptor (IGF1R) but there is still a lack of information regarding the mechanism of IGF binding by IGFBPs. While many studies have defined general regions of the IGFBPs that interact with IGFs, only recently have specific IGF binding residues been described. This review will outline the structural evidence describing residues of both the IGFBPs and IGFs involved in the IGFBP.IGF interaction.Abbreviations: IGF, insulin-like growth factor; IGFBP, IGF binding protein; IGF1R, type 1 IGF receptor; IGF2R, type 2 IGF receptor.

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Section: Structural Evidence For Igfbp Residues Involved In the Igfbpsupporting

confidence: 85%

The interaction of Insulin-like Growth Factors (IGFs) with Insulin-like Growth Factor Binding Proteins (IGFBPs): a review

2001

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“…The binding curve at pH 3·4 was atypical of the high-affinity binding interaction with IGFBP-2, showing more rapid dissociation from IGF-I biosensor surfaces than at pH 4·4 or 5·4. Furthermore, TROSY spectra of the complex at various pH values in (Laajoki et al 2000) and IGF-II (Torres et al 1995) are shown in stereo. The backbone is shown as a ribbon and the side chains as lines.…”

Section: Discussionmentioning

confidence: 99%

Interaction of insulin-like growth factor (IGF)-I and -II with IGF binding protein-2: mapping the binding surfaces by nuclear magnetic resonance

Carrick

Hinds

McNeil

et al. 2005

Journal of Molecular Endocrinology

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The interaction of IGF binding protein-2 (IGFBP-2) with IGF-I and -II has been investigated in solution using nuclear magnetic resonance (NMR) spectroscopy. Chemical shift perturbations in 15 N-and 2 H/ 15 N-labelled IGF-I or -II upon binding to unlabelled thioredoxin-tagged bovine IGFBP-2 (Trx 1-279 IGFBP-2) have been monitored to identify residues involved directly in the binding interaction as well as any affected by conformational changes associated with the interaction. A key step in obtaining high-quality spectra of the complexes was the use of transverse relaxation optimised spectroscopy (TROSY) methods with partially deuterated ligands. Indeed, because the effects of conformational averaging and aggregation are eliminated in IGF-I and -II bound to IGFBP-2, the spectra of the complexes are actually superior to those of the free ligands. Comparison of our results with the crystal structure of the complex between IGF-I and an N-terminal fragment of IGFBP-5 allowed identification of those residues perturbed by the C-domain of IGFBP-2. Other perturbations, such as those of Gly 19 and Asp 20 of IGF-I (and the corresponding residues in IGF-II) -which are located in a reverse turn linking N-domain and C-domain interactive surfaces -are due to local conformational changes in the IGF-I and -II. Our results confirm that the C-domain of IGFBP-2 plays a key role in binding regions of IGF-I and -II that are also involved in binding to the type-1 IGF receptor and thereby blocking ligand binding to this receptor.

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“…In this case, the aryl azide resides near the outer edge of the IGF-1-binding domain, defining the site of contact for Gly 1 . The longer, more flexible side chain present on the aryl azide in bedG 1 IGF-1 has the potential to define a contact site within the vicinity of the other residues of the IGFBPbinding domain, including Glu 3 , which plays an essential role in maintaining high affinity binding to the IGFBPs (43). Although we cannot rule out the possibility that this side chain results in the labeling of regions of the IGFBPs outside the IGF-binding domain, we believe that the likelihood of this occurring is minimal based on the previous identifications of C-terminal binding activity described above.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Characterization of Insulin-like Growth Factor (IGF)-1 Photoprobes Selective for the IGF-binding Proteins (IGFBPs)

Horney

Evangelista

Rosenzweig

2001

Journal of Biological Chemistry

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Solution Structure and Backbone Dynamics of Long-[Arg3]insulin-like Growth Factor-I

Abstract: Long-[Arg 3 ]insulin-like growth factor-I (IGF-I) is a potent analog of insulin-like growth factor-I that has been modified by a Glu

Cited by 24 publications

References 33 publications

The interaction of Insulin-like Growth Factors (IGFs) with Insulin-like Growth Factor Binding Proteins (IGFBPs): a review

The interaction of Insulin-like Growth Factors (IGFs) with Insulin-like Growth Factor Binding Proteins (IGFBPs): a review

Interaction of insulin-like growth factor (IGF)-I and -II with IGF binding protein-2: mapping the binding surfaces by nuclear magnetic resonance

Synthesis and Characterization of Insulin-like Growth Factor (IGF)-1 Photoprobes Selective for the IGF-binding Proteins (IGFBPs)

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