MSOE Sandbox HA
From Proteopedia
| Line 11: | Line 11: | ||
The threat of an influenza pandemic looms eminent in the future of public health around the globe, similar to the previous 1918 H1N1 Spanish flu, 1957 H2N2 Asian flu, and 1968 H3N2 Hong Kong flu epidemics. Synthesizing a broad-spectrum influenza vaccine remains elusive due to the highly mutable nature of the head region of the viral protein hemagglutinin (HA). However, it is known that the stem portion of this molecule is highly stable and that the human antibody CR6261 Fab can dock into a stem region binding site in the presence of low pH to activate the conformational change of HA. This allows the virus to fuse with the membrane of the host cell to initiate the viral infection. The development of a de novo protein molecule that mimics this docking action into the binding site was done computationally, and 88 designs were tested for effectiveness using the yeast strain EBY 100. Following affinity maturation, the 3R2X protein was shown to effectively bind at the conserved surface patch and inhibit the conformational change at low pH. This protocol of producing de novo designed proteins may alleviate the problem of producing sufficient quantities of CR6261 in the event of a pandemic. | The threat of an influenza pandemic looms eminent in the future of public health around the globe, similar to the previous 1918 H1N1 Spanish flu, 1957 H2N2 Asian flu, and 1968 H3N2 Hong Kong flu epidemics. Synthesizing a broad-spectrum influenza vaccine remains elusive due to the highly mutable nature of the head region of the viral protein hemagglutinin (HA). However, it is known that the stem portion of this molecule is highly stable and that the human antibody CR6261 Fab can dock into a stem region binding site in the presence of low pH to activate the conformational change of HA. This allows the virus to fuse with the membrane of the host cell to initiate the viral infection. The development of a de novo protein molecule that mimics this docking action into the binding site was done computationally, and 88 designs were tested for effectiveness using the yeast strain EBY 100. Following affinity maturation, the 3R2X protein was shown to effectively bind at the conserved surface patch and inhibit the conformational change at low pH. This protocol of producing de novo designed proteins may alleviate the problem of producing sufficient quantities of CR6261 in the event of a pandemic. | ||
| + | |||
| + | <scene name='MSOE_Sandbox_HA/Two_chain_of_ha/1'>TextToBeDisplayed</scene> | ||
Revision as of 20:29, 4 August 2011
|
Title: Hemagglutinin Bound to Antibody CR6261 and Bound de novo Protein HB36
Abstract:
The threat of an influenza pandemic looms eminent in the future of public health around the globe, similar to the previous 1918 H1N1 Spanish flu, 1957 H2N2 Asian flu, and 1968 H3N2 Hong Kong flu epidemics. Synthesizing a broad-spectrum influenza vaccine remains elusive due to the highly mutable nature of the head region of the viral protein hemagglutinin (HA). However, it is known that the stem portion of this molecule is highly stable and that the human antibody CR6261 Fab can dock into a stem region binding site in the presence of low pH to activate the conformational change of HA. This allows the virus to fuse with the membrane of the host cell to initiate the viral infection. The development of a de novo protein molecule that mimics this docking action into the binding site was done computationally, and 88 designs were tested for effectiveness using the yeast strain EBY 100. Following affinity maturation, the 3R2X protein was shown to effectively bind at the conserved surface patch and inhibit the conformational change at low pH. This protocol of producing de novo designed proteins may alleviate the problem of producing sufficient quantities of CR6261 in the event of a pandemic.
Proteopedia Page Contributors and Editors (what is this?)
Carla Dee Reedy, Colleen Hampton, Deirdre O'Mara, Judith South Rokous
