PMID: 16169851

 

    Legend: Sugar

Title : Attenuating lymphocyte activity: the crystal structure of the BTLA- HVEM complex

Abstract :

1. Five CD28-like proteins exert positive or negative effects on immune cells
2. Only four of these five receptors interact with members of the B7 family
3. The exception is BTLA ( B and T lymphocyte attenuator ), which instead interacts with the tumor necrosis factor receptor superfamily member HVEM ( herpes virus entry mediator )
4. To better understand this interaction, we determined the 2.8-A crystal structure of the BTLA- HVEM complex
5. This structure shows that BTLA binds the N-terminal cysteine-rich domain of HVEM and employs a unique binding surface compared with other CD28-like receptors
6. Moreover, the structure shows that BTLA recognizes the same surface on HVEM as gD (herpes virus glycoprotein D ) and utilizes a similar binding motif
7. Light scattering analysis demonstrates that the extracellular domain of BTLA is monomeric and that BTLA and HVEM form a 1:1 complex
8. Alanine-scanning mutagenesis of HVEM was used to further define critical binding residues
9. Finally, BTLA adopts an immunoglobulin I-set fold
10. Despite structural similarities to other CD28-like members, BTLA represents a unique co-receptor