Histidine residue modification inhibits binding of murine β nerve growth factor to its receptor

Dunbar, Joan C.; Tregear, Geoffrey W.; Bradshaw, Ralph A.

doi:10.1007/bf01025171

Cited by 13 publications

(18 citation statements)

References 22 publications

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“…We exploited the advantage of the chemical modification of His and availability of the H75A/ H84Q mutant lacking two His residues to directly modify the His-4 and His-8 residues in order to help elucidate the role of these two residues in NGF-receptor interaction. The quantitative DEP modification of His residues in the ␤-NGF preparation was repeated essentially the same as the earlier modification of the 2.5 S NGF (38). The H75A, H84A, and H75A/H84Q mutants were also modified with a 10-fold molar excess of DEP with about 90 -100% of the remaining His residues reacting within 40 min at 25°C as shown by the increased absorbance at 240 nm (data not shown).…”

Section: Expression and Purification Of Recombinant Ngf Histidinementioning

confidence: 78%

“…Chemical modification of the histidine residues of des(1-9)NGF with diethyl pyrocarbonate (DEP) greatly reduced the receptor binding affinity with rabbit superior cervical ganglia, suggesting that His-75 and/or His-84 are responsible for the receptor binding (38). Interestingly, the absence of the two histidines when the NH 2 -terminal region was removed did not affect the sensitivity to DEP modification as measured by binding affinity in these studies.…”

mentioning

confidence: 79%

“…DEP Modification Disrupts Biological Activity and Receptor Binding-Earlier studies of DEP-modified 2.5S NGF and des(1-9)NGF concluded that His-4 and His-8 would be dispensable for receptor binding (38). We exploited the advantage of the chemical modification of His and availability of the H75A/ H84Q mutant lacking two His residues to directly modify the His-4 and His-8 residues in order to help elucidate the role of these two residues in NGF-receptor interaction.…”

Section: Expression and Purification Of Recombinant Ngf Histidinementioning

confidence: 99%

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Characterization of Histidine Residues Essential for Receptor Binding and Activity of Nerve Growth Factor

Woo

Neet

1996

Journal of Biological Chemistry

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Section: Expression and Purification Of Recombinant Ngf Histidinementioning

confidence: 78%

mentioning

confidence: 79%

Section: Expression and Purification Of Recombinant Ngf Histidinementioning

confidence: 99%

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Characterization of Histidine Residues Essential for Receptor Binding and Activity of Nerve Growth Factor

Woo

Neet

1996

Journal of Biological Chemistry

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“…His 84 is conserved in all NGFs except snake, but is glutamine in all other neurotrophins. Modification of NGF with diethylpyrocarbonate resulted in the quantitative modification of the histidine residues with a concomitant loss of binding to rabbit superior cervical ganglia (Dunbar et al, 1984). No significant conformational change accompanied the conversion, as judged by fluorescence spectroscopy, suggesting that the quaternary structure was also not altered (although this was not established directly).…”

Section: Histidinementioning

confidence: 98%

Nerve growth factor: Structure/function relationships

et al. 1994

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Nerve growth factor (NGF), which has a tertiary structure based on a cluster of 3 cystine disulfides and 2 very extended, but distorted 0-hairpins, is the prototype of a larger family of neurotrophins. Prior to the availability of cloning techniques, the mouse submandibular gland was the richest source of NGF and provided sufficient material to enable its biochemical characterization. It binds as a dimer to at least 2 cell-surface receptor types expressed in a variety of neuronal and non-neuronal cells. Residues involved in these interactions and in the maintenance of tertiary and quaternary structure have been identified by chemical modification and site-directed mutagenesis, and this information can be related to their location in the 3-dimensional structure. For example, interactions between aromatic residues contribute to the stability of the NGF dimer, and specific surface lysine residues participate in receptor contacts. The conclusion from these studies is that receptor interactions involve broad surface regions, which may be composed of residues from both protomers in the dimer.Keywords: nerve growth factor; neurotrophins; structure/function relationships The elucidation of the structure/function relationships of a protein requires a precise knowledge of the 3-dimensional structure and the identification of the residues that participate in biological activity. The latter were traditionally defined by chemical modification, which has now been supplanted, to a large degree, by site-directed mutagenesis, primarily because it offers the possibility of making substitutions anywhere in the molecule. However, despite its limitations, chemical modification does offer 1 major advantage: it is carried out on the intact protein and does not generally require refolding, a problem that has hampered the preparation of many recombinant derivatives. As is often the case, both approaches used in concert may provide much more information than either alone.

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“…Chemical modification of His" and Hisg4 (His" and His86, numbering scheme in Fig. 2) of mouse,&NGF also results in a loss of receptor binding [26]; however, these residues are not conseried.…”

Section: Resultsmentioning

confidence: 99%

Comparison of mammalian, chicken and Xenopus brain‐derived neurotrophic factor coding sequences

1991

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We have used the polyrnerase chain reaction (PCR) to amplify and clone coding sequences of the mature region of brain-derived neurotrophic factor (BDNF) from monkey, rat, chicken and XenopuF genomic DNA. Consistent with previous reports, the predicted amino acid sequences obtained in this manner from monkey and rat were identi c?J !o other mammalian BDNF sequences. 'The chicken and Xenopus BDNF sequences arc also highly conserved, but contain 7 and 8 amix acid substitutions, respectively, compared to mammalian BDNF. Comparison of these sequences with the homologous NGF and NT3 coding .r..'ions provides further insight into amino acid residues that may be responsible for the differenl receptor specificities of these factors.

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Histidine residue modification inhibits binding of murine β nerve growth factor to its receptor

Cited by 13 publications

References 22 publications

Characterization of Histidine Residues Essential for Receptor Binding and Activity of Nerve Growth Factor

Characterization of Histidine Residues Essential for Receptor Binding and Activity of Nerve Growth Factor

Nerve growth factor: Structure/function relationships

Comparison of mammalian, chicken and Xenopus brain‐derived neurotrophic factor coding sequences

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