A discrete domain of the human TrkB receptor defines the binding sites for BDNF and NT-4.
TrkB is a member of the Trk family of tyrosine kinase receptors. In vivo, the extracellular region of TrkB is known to bind, with high affinity, the neurotrophin protein brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4). We describe the expression and purification of the second Ig-l...
| Main Authors: | , , , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado: |
2002
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| _version_ | 1826281714418188288 |
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| author | Naylor, R Robertson, A Allen, S Sessions, R Clarke, A Mason, G Burston, J Tyler, S Wilcock, G Dawbarn, D |
| author_facet | Naylor, R Robertson, A Allen, S Sessions, R Clarke, A Mason, G Burston, J Tyler, S Wilcock, G Dawbarn, D |
| author_sort | Naylor, R |
| collection | OXFORD |
| description | TrkB is a member of the Trk family of tyrosine kinase receptors. In vivo, the extracellular region of TrkB is known to bind, with high affinity, the neurotrophin protein brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4). We describe the expression and purification of the second Ig-like domain of human TrkB (TrkBIg(2)) and show, using surface plasmon resonance, that this domain is sufficient to bind BDNF and NT-4 with subnanomolar affinity. BDNF and NT-4 may have therapeutic implications for a variety of neurodegenerative diseases. The specificity of binding of the neurotrophins to their receptor TrkB is therefore of interest. We examine the specificity of TrkBIg(2) for all the neurotrophins, and use our molecular model of the BDNF-TrkBIg(2) complex to examine the residues involved in binding. It is hoped that the understanding of specific interactions will allow design of small molecule neurotrophin mimetics. |
| first_indexed | 2024-03-07T00:32:57Z |
| format | Journal article |
| id | oxford-uuid:8071e6e6-a4f4-46e9-bd63-59e6c6ec096b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:32:57Z |
| publishDate | 2002 |
| record_format | dspace |
| spelling | oxford-uuid:8071e6e6-a4f4-46e9-bd63-59e6c6ec096b2022-03-26T21:23:21ZA discrete domain of the human TrkB receptor defines the binding sites for BDNF and NT-4.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8071e6e6-a4f4-46e9-bd63-59e6c6ec096bEnglishSymplectic Elements at Oxford2002Naylor, RRobertson, AAllen, SSessions, RClarke, AMason, GBurston, JTyler, SWilcock, GDawbarn, DTrkB is a member of the Trk family of tyrosine kinase receptors. In vivo, the extracellular region of TrkB is known to bind, with high affinity, the neurotrophin protein brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4). We describe the expression and purification of the second Ig-like domain of human TrkB (TrkBIg(2)) and show, using surface plasmon resonance, that this domain is sufficient to bind BDNF and NT-4 with subnanomolar affinity. BDNF and NT-4 may have therapeutic implications for a variety of neurodegenerative diseases. The specificity of binding of the neurotrophins to their receptor TrkB is therefore of interest. We examine the specificity of TrkBIg(2) for all the neurotrophins, and use our molecular model of the BDNF-TrkBIg(2) complex to examine the residues involved in binding. It is hoped that the understanding of specific interactions will allow design of small molecule neurotrophin mimetics. |
| spellingShingle | Naylor, R Robertson, A Allen, S Sessions, R Clarke, A Mason, G Burston, J Tyler, S Wilcock, G Dawbarn, D A discrete domain of the human TrkB receptor defines the binding sites for BDNF and NT-4. |
| title | A discrete domain of the human TrkB receptor defines the binding sites for BDNF and NT-4. |
| title_full | A discrete domain of the human TrkB receptor defines the binding sites for BDNF and NT-4. |
| title_fullStr | A discrete domain of the human TrkB receptor defines the binding sites for BDNF and NT-4. |
| title_full_unstemmed | A discrete domain of the human TrkB receptor defines the binding sites for BDNF and NT-4. |
| title_short | A discrete domain of the human TrkB receptor defines the binding sites for BDNF and NT-4. |
| title_sort | discrete domain of the human trkb receptor defines the binding sites for bdnf and nt 4 |
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