11:14 〜 11:28
[WS4-07] Smallpox virus chemokine-binding proteins have strong anti-inflammatory properties
Poxviruses are the source for dozens of immune modulating proteins that target many aspects of immunity. Given that smallpox “immune evasion” proteins have been honed through evolution to affect the human immune response with few off-target effects, it is expected that they would have strong human anti-inflammatory properties.
We have studied one of these proteins, G3R – a chemokine binding protein (CKBP), to delineate the range and affinity of its binding to chemokines. G3R binds broadly to CC class chemokines with picomolar affinity, however, its binding range crosses over into other chemokine classes, with binding noted to fractalkine (hCX3CL1) and lymphotactin (XCL1) among others.
Purified G3R crystallises with some coaxing in Space Group P21. These crystals diffract to 2Å but decay rapidly in the X-ray beam even while frozen. The completed crystal structure resembles other poxvirus immune evasion proteins (PIEs) with a β-sandwich fold, and with prominent but polarized β-sheet surfaces that are useful in modelling the likely structural basis for chemokine-chemokine binding protein interactions.
We have studied one of these proteins, G3R – a chemokine binding protein (CKBP), to delineate the range and affinity of its binding to chemokines. G3R binds broadly to CC class chemokines with picomolar affinity, however, its binding range crosses over into other chemokine classes, with binding noted to fractalkine (hCX3CL1) and lymphotactin (XCL1) among others.
Purified G3R crystallises with some coaxing in Space Group P21. These crystals diffract to 2Å but decay rapidly in the X-ray beam even while frozen. The completed crystal structure resembles other poxvirus immune evasion proteins (PIEs) with a β-sandwich fold, and with prominent but polarized β-sheet surfaces that are useful in modelling the likely structural basis for chemokine-chemokine binding protein interactions.