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291 Construction and Biological Function of the gp120 Bridging Sheet
C. H. Chen* and C. B. Zhu
Meharry Med. Coll., Nashville, TN, USA
The bridging sheet of HIV-1 gp120 is a relatively conserved structural motif that is proposed to be involved in the interaction between gp120 and chemokine receptors. The bridging sheet contains 4 anti-parallel beta sheets from discontinuous regions of gp120. To study the biological function and potential to induce neutralizing antibodies, we have attempted to construct and express a bridging sheet mimetic in bacteria. The purified bridging sheet mimetic reacts well with neutralizing antibodies such as 17b. The conformational monoclonal antibody 17b was previously reported to have multiple contacts with all of the 4 beta sheets of the bridging sheet. The ability of the bridging sheet mimetic to react with this conformational antibody suggests that the bacterial recombinant protein retains at least certain fractions of the authentic bridging sheet structure. The bridging sheet mimetic binds weakly to chemokine receptors on cell surface. The direct binding of the bridging sheet mimetic to chemokine receptors suggests that the bridging sheet might be important for HIV-1 entry. The effect of the bridging sheet mimetic on HIV-1 entry will be discussed.
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