1lmk
From Proteopedia
(New page: 200px<br /> <applet load="1lmk" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lmk, resolution 2.6Å" /> '''THE STRUCTURE OF A B...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1lmk.gif|left|200px]]<br /> | + | [[Image:1lmk.gif|left|200px]]<br /><applet load="1lmk" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1lmk" size=" | + | |
caption="1lmk, resolution 2.6Å" /> | caption="1lmk, resolution 2.6Å" /> | ||
'''THE STRUCTURE OF A BIVALENT DIABODY'''<br /> | '''THE STRUCTURE OF A BIVALENT DIABODY'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Diabodies are dimeric antibody fragments. In each polypeptide, a heavy-chain variable domain (VH) is linked to a light-chain variable | + | BACKGROUND: Diabodies are dimeric antibody fragments. In each polypeptide, a heavy-chain variable domain (VH) is linked to a light-chain variable domain (VL) but unlike single-chain Fv fragments, each antigen-binding site is formed by pairing of one VH and one VL domain from the two different polypeptides. Diabodies thus have two antigen-binding sites, and can be bispecific. Direct structural evidence is lacking for the connections and dimeric interactions between the two polypeptides of the diabody. RESULTS: The 2.6 A resolution structure has been determined for a bivalent diabody with a flexible five-residue polypeptide linker between the (amino-terminal) VH and (carboxy-terminal) VL domains. The asymmetric unit of the crystal consists of four polypeptides comprising two diabodies; for one of these polypeptides the linker can be traced between the VH and VL domains. Within each diabody the two associated VH and VL domains make back-to-back interactions through the VH domains, and there is an extensive VL-VL interface between the two diabodies in the asymmetric unit. CONCLUSIONS: The structure of the diabody is very similar to that which had been predicted by molecular modelling. Diabodies directed against cell-surface antigens should be capable of bringing together two cells, such as in cell-targeted therapy, because the two antigen-binding sites of the diabody are at opposite ends of the molecule and separated by approximately 65 A. |
==About this Structure== | ==About this Structure== | ||
| - | 1LMK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http:// | + | 1LMK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LMK OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 13: | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Williams, R | + | [[Category: Williams, R L.]] |
[[Category: immunoglobulin]] | [[Category: immunoglobulin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:46:21 2008'' |
Revision as of 11:46, 21 February 2008
|
THE STRUCTURE OF A BIVALENT DIABODY
Overview
BACKGROUND: Diabodies are dimeric antibody fragments. In each polypeptide, a heavy-chain variable domain (VH) is linked to a light-chain variable domain (VL) but unlike single-chain Fv fragments, each antigen-binding site is formed by pairing of one VH and one VL domain from the two different polypeptides. Diabodies thus have two antigen-binding sites, and can be bispecific. Direct structural evidence is lacking for the connections and dimeric interactions between the two polypeptides of the diabody. RESULTS: The 2.6 A resolution structure has been determined for a bivalent diabody with a flexible five-residue polypeptide linker between the (amino-terminal) VH and (carboxy-terminal) VL domains. The asymmetric unit of the crystal consists of four polypeptides comprising two diabodies; for one of these polypeptides the linker can be traced between the VH and VL domains. Within each diabody the two associated VH and VL domains make back-to-back interactions through the VH domains, and there is an extensive VL-VL interface between the two diabodies in the asymmetric unit. CONCLUSIONS: The structure of the diabody is very similar to that which had been predicted by molecular modelling. Diabodies directed against cell-surface antigens should be capable of bringing together two cells, such as in cell-targeted therapy, because the two antigen-binding sites of the diabody are at opposite ends of the molecule and separated by approximately 65 A.
About this Structure
1LMK is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
Reference
Crystal structure of a diabody, a bivalent antibody fragment., Perisic O, Webb PA, Holliger P, Winter G, Williams RL, Structure. 1994 Dec 15;2(12):1217-26. PMID:7704531
Page seeded by OCA on Thu Feb 21 13:46:21 2008
