1jge
From Proteopedia
(New page: 200px<br /> <applet load="1jge" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jge, resolution 2.1Å" /> '''HLA-B*2705 bound to ...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1jge.gif|left|200px]]<br /> | + | [[Image:1jge.gif|left|200px]]<br /><applet load="1jge" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1jge" size=" | + | |
caption="1jge, resolution 2.1Å" /> | caption="1jge, resolution 2.1Å" /> | ||
'''HLA-B*2705 bound to nona-peptide m9'''<br /> | '''HLA-B*2705 bound to nona-peptide m9'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The reasons for the association of the human major histocompatibility | + | The reasons for the association of the human major histocompatibility complex protein HLA-B27 with spondyloarthropathies are unknown. To uncover the underlying molecular causes, we determined the crystal structures of the disease-associated B*2705 and the nonassociated B*2709 subtypes complexed with the same nonapeptide (GRFAAAIAK). Both differ in only one residue (Asp(116) and His(116), respectively) in the F-pocket that accommodates the peptide C terminus. Several different effects of the Asp(116) --> His replacement are observed. The bulkier His(116) induces a movement of peptide C-terminal pLys(9), allowing the formation of a novel salt bridge to Asp(77), whereas the salt bridge between pLys(9) and Asp(116) is converted into a hydrogen bond with His(116). His(116) but not Asp(116) adopts two alternative conformations, one of which leads to breakage of hydrogen bonds. Water molecules near residue 116 differ with regard to number, position, and contacts made. Furthermore, F-pocket atoms exhibit higher B-factors in B*2709 than in B*2705, indicating an increased flexibility of the entire region in the former subtype. These changes induce subtle peptide conformational alterations that may be responsible for the immunobiological differences between these HLA-B27 subtypes. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1JGE is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1JGE is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JGE OCA]. |
==Reference== | ==Reference== | ||
| Line 17: | Line 16: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Hillig, R | + | [[Category: Hillig, R C.]] |
[[Category: Hulsmeyer, M.]] | [[Category: Hulsmeyer, M.]] | ||
[[Category: Ruhl, M.]] | [[Category: Ruhl, M.]] | ||
| Line 28: | Line 27: | ||
[[Category: mhc (major histocompatibility complex)]] | [[Category: mhc (major histocompatibility complex)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:22:29 2008'' |
Revision as of 11:22, 21 February 2008
|
HLA-B*2705 bound to nona-peptide m9
Contents |
Overview
The reasons for the association of the human major histocompatibility complex protein HLA-B27 with spondyloarthropathies are unknown. To uncover the underlying molecular causes, we determined the crystal structures of the disease-associated B*2705 and the nonassociated B*2709 subtypes complexed with the same nonapeptide (GRFAAAIAK). Both differ in only one residue (Asp(116) and His(116), respectively) in the F-pocket that accommodates the peptide C terminus. Several different effects of the Asp(116) --> His replacement are observed. The bulkier His(116) induces a movement of peptide C-terminal pLys(9), allowing the formation of a novel salt bridge to Asp(77), whereas the salt bridge between pLys(9) and Asp(116) is converted into a hydrogen bond with His(116). His(116) but not Asp(116) adopts two alternative conformations, one of which leads to breakage of hydrogen bonds. Water molecules near residue 116 differ with regard to number, position, and contacts made. Furthermore, F-pocket atoms exhibit higher B-factors in B*2709 than in B*2705, indicating an increased flexibility of the entire region in the former subtype. These changes induce subtle peptide conformational alterations that may be responsible for the immunobiological differences between these HLA-B27 subtypes.
Disease
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142830], Hypoproteinemia, hypercatabolic OMIM:[109700], Spondyloarthropathy, susceptibility to, 1 OMIM:[142830], Stevens-Johnson syndrome, carbamazepine-induced, susceptibility to OMIM:[142830]
About this Structure
1JGE is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
HLA-B27 subtypes differentially associated with disease exhibit subtle structural alterations., Hulsmeyer M, Hillig RC, Volz A, Ruhl M, Schroder W, Saenger W, Ziegler A, Uchanska-Ziegler B, J Biol Chem. 2002 Dec 6;277(49):47844-53. Epub 2002 Sep 18. PMID:12244049
Page seeded by OCA on Thu Feb 21 13:22:29 2008
