6XRX

Crystal structure of the mosquito protein AZ1 as an MBP fusion

Summary for 6XRX

• Entry DOI: 10.2210/pdb6xrx/pdb
• Related PRD ID: PRD_900001
• Descriptor: Maltose/maltodextrin-binding periplasmic protein, Mosquito protein AZ1, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, SODIUM ION, ... (6 entities in total)
• Functional Keywords: mosquito, fatty acids, lipids, anti-viral, lipid binding protein
• Biological source: Escherichia coli; More
• Total number of polymer chains: 1
• Total formula weight: 61850.49

Authors

Pedersen, L.C.,Mueller, G.A.,Foo, A.C.Y. (deposition date: 2020-07-14, release date: 2021-03-24, Last modification date: 2023-10-18)

Primary citation

Foo, A.C.Y.,Thompson, P.M.,Chen, S.H.,Jadi, R.,Lupo, B.,DeRose, E.F.,Arora, S.,Placentra, V.C.,Premkumar, L.,Perera, L.,Pedersen, L.C.,Martin, N.,Mueller, G.A.
The mosquito protein AEG12 displays both cytolytic and antiviral properties via a common lipid transfer mechanism.
Proc.Natl.Acad.Sci.USA, 118:-, 2021

PubMed Abstract: The mosquito protein AEG12 is up-regulated in response to blood meals and flavivirus infection though its function remained elusive. Here, we determine the three-dimensional structure of AEG12 and describe the binding specificity of acyl-chain ligands within its large central hydrophobic cavity. We show that AEG12 displays hemolytic and cytolytic activity by selectively delivering unsaturated fatty acid cargoes into phosphatidylcholine-rich lipid bilayers. This property of AEG12 also enables it to inhibit replication of enveloped viruses such as Dengue and Zika viruses at low micromolar concentrations. Weaker inhibition was observed against more distantly related coronaviruses and lentivirus, while no inhibition was observed against the nonenveloped virus adeno-associated virus. Together, our results uncover the mechanistic understanding of AEG12 function and provide the necessary implications for its use as a broad-spectrum therapeutic against cellular and viral targets.

PubMed: 33688047
DOI: 10.1073/pnas.2019251118

Experimental method

X-RAY DIFFRACTION (1.95 Å)