An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly.
Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2010
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| _version_ | 1797057023015124992 |
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| author | Seiradake, E Harlos, K Sutton, G Aricescu, A Jones, E |
| author_facet | Seiradake, E Harlos, K Sutton, G Aricescu, A Jones, E |
| author_sort | Seiradake, E |
| collection | OXFORD |
| description | Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays. |
| first_indexed | 2024-03-06T19:30:35Z |
| format | Journal article |
| id | oxford-uuid:1d538a14-286e-4f9e-91aa-cc526af51e59 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:30:35Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:1d538a14-286e-4f9e-91aa-cc526af51e592022-03-26T11:10:11ZAn extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1d538a14-286e-4f9e-91aa-cc526af51e59EnglishSymplectic Elements at Oxford2010Seiradake, EHarlos, KSutton, GAricescu, AJones, EErythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays. |
| spellingShingle | Seiradake, E Harlos, K Sutton, G Aricescu, A Jones, E An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly. |
| title | An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly. |
| title_full | An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly. |
| title_fullStr | An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly. |
| title_full_unstemmed | An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly. |
| title_short | An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly. |
| title_sort | extracellular steric seeding mechanism for eph ephrin signaling platform assembly |
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