1uuh
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1uuh |SIZE=350|CAPTION= <scene name='initialview01'>1uuh</scene>, resolution 2.200Å | |PDB= 1uuh |SIZE=350|CAPTION= <scene name='initialview01'>1uuh</scene>, resolution 2.200Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1uuh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uuh OCA], [http://www.ebi.ac.uk/pdbsum/1uuh PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1uuh RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Blood group, Indian system OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107269 107269]], Fertile eunuch syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=138850 138850]], Hypogonadotropic hypogonadism OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=138850 138850]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 45: | Line 45: | ||
[[Category: sugar-binding]] | [[Category: sugar-binding]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:15:27 2008'' |
Revision as of 21:15, 30 March 2008
| |||||||
| , resolution 2.200Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HYALURONAN BINDING DOMAIN OF HUMAN CD44
Overview
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.
About this Structure
1UUH is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of the regulatory hyaluronan binding domain in the inflammatory leukocyte homing receptor CD44., Teriete P, Banerji S, Noble M, Blundell CD, Wright AJ, Pickford AR, Lowe E, Mahoney DJ, Tammi MI, Kahmann JD, Campbell ID, Day AJ, Jackson DG, Mol Cell. 2004 Feb 27;13(4):483-96. PMID:14992719
Page seeded by OCA on Mon Mar 31 00:15:27 2008
Categories: Homo sapiens | Single protein | Banerji, S. | Blundell, C. | Campbell, I. | Day, A. | Jackson, D. | Kahmann, J. | Lowe, E. | Mahoney, D. | Noble, M. | Pickford, A. | Tammi, M. | Teriete, P. | Wright, A. | C-type lectin | Extracellular matrix | Hyaluronan | Link-domain | Receptor | Sugar-binding
