1gp9
From Proteopedia
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|PDB= 1gp9 |SIZE=350|CAPTION= <scene name='initialview01'>1gp9</scene>, resolution 2.50Å | |PDB= 1gp9 |SIZE=350|CAPTION= <scene name='initialview01'>1gp9</scene>, resolution 2.50Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID'>EPE</scene> | + | |LIGAND= <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1gp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gp9 OCA], [http://www.ebi.ac.uk/pdbsum/1gp9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1gp9 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
NK1 is a splice variant of the polypeptide growth factor HGF/SF that consists of the N terminal (N) and first kringle (K) domains and retains receptor binding and signalling. While NK1 behaves as a monomer in solution, two independent crystallographic structures have previously shown an identical, tightly packed dimer. Here we report a novel orthorhombic crystal form of NK1 at 2.5 A resolution in which four NK1 protomers are packed in two distinct dimers in the asymmetric unit. Although the basic architecture of the new NK1 dimers is similar to the two described earlier, the new crystal form demonstrates extensive hinge movement between the N and K domain that leads to re-orientation of the receptor-binding sites. The hinge bending is evidence of the paucity of strong interactions between domains within the protomer, in contrast to the extensive interactions between protomers in the dimer. These observations are consistent with domain swapping in the dimer, such that the interdomain interactions of the monomer are replaced by equivalent interprotomer interactions in the dimer and offer a route for protein engineering of NK1 variants which may act as receptor antagonists. | NK1 is a splice variant of the polypeptide growth factor HGF/SF that consists of the N terminal (N) and first kringle (K) domains and retains receptor binding and signalling. While NK1 behaves as a monomer in solution, two independent crystallographic structures have previously shown an identical, tightly packed dimer. Here we report a novel orthorhombic crystal form of NK1 at 2.5 A resolution in which four NK1 protomers are packed in two distinct dimers in the asymmetric unit. Although the basic architecture of the new NK1 dimers is similar to the two described earlier, the new crystal form demonstrates extensive hinge movement between the N and K domain that leads to re-orientation of the receptor-binding sites. The hinge bending is evidence of the paucity of strong interactions between domains within the protomer, in contrast to the extensive interactions between protomers in the dimer. These observations are consistent with domain swapping in the dimer, such that the interdomain interactions of the monomer are replaced by equivalent interprotomer interactions in the dimer and offer a route for protein engineering of NK1 variants which may act as receptor antagonists. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Fibromatosis, gingival OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=182530 182530]], Noonan syndrome 4 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=182530 182530]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Lietha, D.]] | [[Category: Lietha, D.]] | ||
[[Category: Watanabe, K.]] | [[Category: Watanabe, K.]] | ||
| - | [[Category: EPE]] | ||
[[Category: domain swapping]] | [[Category: domain swapping]] | ||
[[Category: glycoprotein]] | [[Category: glycoprotein]] | ||
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[[Category: protein engineering]] | [[Category: protein engineering]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:48:37 2008'' |
Revision as of 17:48, 30 March 2008
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| , resolution 2.50Å | |||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
A NEW CRYSTAL FORM OF THE NK1 SPLICE VARIANT OF HGF/SF DEMONSTRATES EXTENSIVE HINGE MOVEMENT AND SUGGESTS THAT THE NK1 DIMER ORIGINATES BY DOMAIN SWAPPING
Overview
NK1 is a splice variant of the polypeptide growth factor HGF/SF that consists of the N terminal (N) and first kringle (K) domains and retains receptor binding and signalling. While NK1 behaves as a monomer in solution, two independent crystallographic structures have previously shown an identical, tightly packed dimer. Here we report a novel orthorhombic crystal form of NK1 at 2.5 A resolution in which four NK1 protomers are packed in two distinct dimers in the asymmetric unit. Although the basic architecture of the new NK1 dimers is similar to the two described earlier, the new crystal form demonstrates extensive hinge movement between the N and K domain that leads to re-orientation of the receptor-binding sites. The hinge bending is evidence of the paucity of strong interactions between domains within the protomer, in contrast to the extensive interactions between protomers in the dimer. These observations are consistent with domain swapping in the dimer, such that the interdomain interactions of the monomer are replaced by equivalent interprotomer interactions in the dimer and offer a route for protein engineering of NK1 variants which may act as receptor antagonists.
About this Structure
1GP9 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
A new crystal form of the NK1 splice variant of HGF/SF demonstrates extensive hinge movement and suggests that the NK1 dimer originates by domain swapping., Watanabe K, Chirgadze DY, Lietha D, de Jonge H, Blundell TL, Gherardi E, J Mol Biol. 2002 May 31;319(2):283-8. PMID:12051906
Page seeded by OCA on Sun Mar 30 20:48:37 2008
