Research in the P. LiWang Group
School of Natural Sciences
University of California, Merced
The overall theme of our laboratory’s research is to study proteins at the molecular level using biochemical analyses alongside powerful tools such as nuclear magnetic resonance (NMR). This includes not only structure determination, but also biological assays of proteins and their mutants in order to understand the structural underpinnings of biological function. We often work with members of the chemokine family of proteins, which are inflammatory proteins, several of which have been shown to block infection by HIV-1, making an analysis of their action crucial for AIDS research. Most recently we have made an extremely potent HIV inhibitor against both R5 and X4 virus using the RANTES variant 5P12-RANTES (originally discovered by the Hartley group) linked to a C-peptide.
We also have a long-standing interest in saccharide binding, leading to our ongoing work with the potent HIV entry inhibitor griffithsin. We have linked this protein with a C-peptide, leading to even more potent HIV inhibition, and are also studying the details of the biochemical properties of griffithsin.
Our work with chemokines and chemokine binding proteins also includes a study of how to inhibit the chemokine system to stop inflammation. This work includes both the proteins vMIP-II and vCCI (see right side for papers on both proteins).
Overall, we use a combination of mutagenesis, NMR techniques, cellular assays, and HIV assays to learn about chemokines and chemokine binding proteins, and to elucidate their role in inflammation and suppressing HIV-1 infection. Links to some of our projects can be found at the right side of this page.
Coming soon: exciting results on the chemokine binding protein vCCI and also on further studies with potent anti-HIV proteins.
We have studied the individual carbohydrate binding sites of the antiviral lectin Griffithsin. This starts several projects that investigate the mechanism of this lectin in its potent anti-HIV activity.
We have linked the chemokine variant 5P12-RANTES with a C-peptide to obtain a chimeric protein that is highly potent against both R5 and X4 tropic HIV. This may be the best HIV entry inhibitor yet reported.
We have found that covalently linking a gp120-binding protein such as griffithsin with a gp41-binding peptide (C37) leads to a more highly potent HIV entry inhibitor than either component separately or in combination.
We have studied the glycosaminoglycan binding properties of the anti-inflammatory chemokine homolog vMIP-II, and also studied a dimeric form of this protein.
Here is a Keystone Symposia abstract for 2010. More details about this work will be put on the web site when the paper(s) are in press.
We have recently determined the structure and carried out functional assays on P2-RANTES, a highly potent HIV inhibitor.
We have used NMR and cellular assays to show definitively that the dimer form of the CC chemokine MIP-1b is not competent to bind the receptor CCR5
We have recently determined the structure of the vCCI:MIP-1b complex by NMR. vCCI is a chemokine binding protein with potent anti-inflammatory properties.
We have used NMR to delinate the glycosaminoglycan binding site on MIP-1b
In addition, we have demonstrated that GAGs tighten the dimer of MIP-1b and RANTES by at least 6 fold.
Another project in lab is research aimed at understanding the differences in quaternary structure between chemokines from different subfamilies