Structure of the regulatory hyaluronan binding domain in the inflammatory leukocyte homing receptor CD44.
Adhesive interactions involving CD44, the cell surface receptor for hyaluronan, underlie fundamental processes such as inflammatory leukocyte homing and tumor metastasis. Regulation of such events is critical and appears to be effected by changes in CD44 N-glycosylation that switch the receptor &quo...
| Päätekijät: | , , , , , , , , , , , , |
|---|---|
| Aineistotyyppi: | Journal article |
| Kieli: | English |
| Julkaistu: |
2004
|
| _version_ | 1826275882957799424 |
|---|---|
| author | Teriete, P Banerji, S Noble, M Blundell, C Wright, A Pickford, A Lowe, E Mahoney, D Tammi, M Kahmann, J Campbell, I Day, A Jackson, D |
| author_facet | Teriete, P Banerji, S Noble, M Blundell, C Wright, A Pickford, A Lowe, E Mahoney, D Tammi, M Kahmann, J Campbell, I Day, A Jackson, D |
| author_sort | Teriete, P |
| collection | OXFORD |
| description | Adhesive interactions involving CD44, the cell surface receptor for hyaluronan, underlie fundamental processes such as inflammatory leukocyte homing and tumor metastasis. Regulation of such events is critical and appears to be effected by changes in CD44 N-glycosylation that switch the receptor "on" or "off" under appropriate circumstances. How altered glycosylation influences binding of hyaluronan to the lectin-like Link module in CD44 is unclear, although evidence suggests additional flanking sequences peculiar to CD44 may be involved. Here we show using X-ray crystallography and NMR spectroscopy that these sequences form a lobular extension to the Link module, creating an enlarged HA binding domain and a formerly unidentified protein fold. Moreover, the disposition of key N-glycosylation sites reveals how specific sugar chains could alter both the affinity and avidity of CD44 HA binding. Our results provide the necessary structural framework for understanding the diverse functions of CD44 and developing novel therapeutic strategies. |
| first_indexed | 2024-03-06T23:05:35Z |
| format | Journal article |
| id | oxford-uuid:63ad26c7-6c8e-464d-a7b6-d9e7dce37ccc |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:05:35Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:63ad26c7-6c8e-464d-a7b6-d9e7dce37ccc2022-03-26T18:14:29ZStructure of the regulatory hyaluronan binding domain in the inflammatory leukocyte homing receptor CD44.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:63ad26c7-6c8e-464d-a7b6-d9e7dce37cccEnglishSymplectic Elements at Oxford2004Teriete, PBanerji, SNoble, MBlundell, CWright, APickford, ALowe, EMahoney, DTammi, MKahmann, JCampbell, IDay, AJackson, DAdhesive interactions involving CD44, the cell surface receptor for hyaluronan, underlie fundamental processes such as inflammatory leukocyte homing and tumor metastasis. Regulation of such events is critical and appears to be effected by changes in CD44 N-glycosylation that switch the receptor "on" or "off" under appropriate circumstances. How altered glycosylation influences binding of hyaluronan to the lectin-like Link module in CD44 is unclear, although evidence suggests additional flanking sequences peculiar to CD44 may be involved. Here we show using X-ray crystallography and NMR spectroscopy that these sequences form a lobular extension to the Link module, creating an enlarged HA binding domain and a formerly unidentified protein fold. Moreover, the disposition of key N-glycosylation sites reveals how specific sugar chains could alter both the affinity and avidity of CD44 HA binding. Our results provide the necessary structural framework for understanding the diverse functions of CD44 and developing novel therapeutic strategies. |
| spellingShingle | Teriete, P Banerji, S Noble, M Blundell, C Wright, A Pickford, A Lowe, E Mahoney, D Tammi, M Kahmann, J Campbell, I Day, A Jackson, D Structure of the regulatory hyaluronan binding domain in the inflammatory leukocyte homing receptor CD44. |
| title | Structure of the regulatory hyaluronan binding domain in the inflammatory leukocyte homing receptor CD44. |
| title_full | Structure of the regulatory hyaluronan binding domain in the inflammatory leukocyte homing receptor CD44. |
| title_fullStr | Structure of the regulatory hyaluronan binding domain in the inflammatory leukocyte homing receptor CD44. |
| title_full_unstemmed | Structure of the regulatory hyaluronan binding domain in the inflammatory leukocyte homing receptor CD44. |
| title_short | Structure of the regulatory hyaluronan binding domain in the inflammatory leukocyte homing receptor CD44. |
| title_sort | structure of the regulatory hyaluronan binding domain in the inflammatory leukocyte homing receptor cd44 |
| work_keys_str_mv | AT terietep structureoftheregulatoryhyaluronanbindingdomainintheinflammatoryleukocytehomingreceptorcd44 AT banerjis structureoftheregulatoryhyaluronanbindingdomainintheinflammatoryleukocytehomingreceptorcd44 AT noblem structureoftheregulatoryhyaluronanbindingdomainintheinflammatoryleukocytehomingreceptorcd44 AT blundellc structureoftheregulatoryhyaluronanbindingdomainintheinflammatoryleukocytehomingreceptorcd44 AT wrighta structureoftheregulatoryhyaluronanbindingdomainintheinflammatoryleukocytehomingreceptorcd44 AT pickforda structureoftheregulatoryhyaluronanbindingdomainintheinflammatoryleukocytehomingreceptorcd44 AT lowee structureoftheregulatoryhyaluronanbindingdomainintheinflammatoryleukocytehomingreceptorcd44 AT mahoneyd structureoftheregulatoryhyaluronanbindingdomainintheinflammatoryleukocytehomingreceptorcd44 AT tammim structureoftheregulatoryhyaluronanbindingdomainintheinflammatoryleukocytehomingreceptorcd44 AT kahmannj structureoftheregulatoryhyaluronanbindingdomainintheinflammatoryleukocytehomingreceptorcd44 AT campbelli structureoftheregulatoryhyaluronanbindingdomainintheinflammatoryleukocytehomingreceptorcd44 AT daya structureoftheregulatoryhyaluronanbindingdomainintheinflammatoryleukocytehomingreceptorcd44 AT jacksond structureoftheregulatoryhyaluronanbindingdomainintheinflammatoryleukocytehomingreceptorcd44 |