VRC01 gp120 complex: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
No edit summary
No edit summary
Line 1: Line 1:
The crystal structure of ToxT is resolved in monomeric form, after isolation from <i>Vibrio cholerae</i> strain O395.<ref name="structure">PMID: 20133655</ref>
The crystal structure of ToxT is resolved in monomeric form, after isolation from <i>Vibrio cholerae</i> strain O395.<ref name="structure">PMID: 20133655</ref>
==Introduction==
==Introduction==
<b>ToxT</b> is a molecule at the end of a transcriptional cascade that autoregulates the transcription of the primary virulence factors of <i>Vibrio cholerae</i>[http://en.wikipedia.org/wiki/Vibrio_cholerae] and itself. ToxT is a cytoplasmic protein that is activated in turn by ToxR, which is itself activated by ToxS in response to environmental stimuli.<ref>Kenneth Todar [http://www.textbookofbacteriology.net/cholera.html] ''Vibrio cholerae'' and Asiatic Cholera, Todar's Online Textbook of Bacteriology. Date of access: 2011-11-28.</ref> These two factors, cholera toxin (CT)[http://en.wikipedia.org/wiki/Cholera_toxin] and the toxin co-regulated pilus (TCP), are instrumental in causing the disease <b>cholera</b>[http://en.wikipedia.org/wiki/Cholera]. This is an intestinal infection resulting in massive water loss in the affected individual, causing extreme dehydration.[http://en.wikipedia.org/wiki/Cholera] Rehydration is sufficient as treatment.
HIV-1 has a high level of antigenic and genetic diversity.  HIV-1 has also evolved mechanisms to evade the humoral immune response.  These aspects of HIV-1 have made it difficult to develop a vaccine.  After several years of infection, 10 to 25% of HIV-1 infected individuals develop neutralizing antibodies.  Some antibodies target the transmembrane gp41 molecules of the HIV-1 viral spike, however most target the surface protein gp120. (Wu) VRC01 and VRC01-like antibodies bind to gp120 and are able to neutralize about 90% of HIV-1 isolates. Structural analysis has shown which characteristics of antibodies are essential to its binding with gp120. (Kwong)  Discovery of the structure of these antibodies can help develop an effective HIV-1 vaccine.
 
==HIV-1 Neutralization==
HIV-1 enters its host by binding viral gp120, a surface glycoprotein of HIV, to the host cell’s CD4 receptor. This interaction induces conformational changes in gp120. (Wu) This conformational change results in the exposure of epitopes that can be bound by co-receptors, usually chemokine receptors. The conformational changes also result in the formation of a pre-hairpin intermediate conformation in which gp41, a transmembrane glycoprotein of HIV, rearranges its molecules so that its N-terminal peptides form a trimer of helices that present a fusion peptide to the target cell.  Once fusion occurs between the fusion peptide and the target cell membrane, HIV is able to enter and infect the target cell. (Tran) VRC01 binds to CD4’s binding site on gp120, preventing the CD4 receptor from binding to HIV and infecting the cell. (Wu).
 
<StructureSection load='3SE9' color='structure' size='500' frame='true' align='right' caption='ToxT complex with palmitoleic acid, 1.9 Angstrom resolution crystal structure, [[3gbg]]' >
<StructureSection load='3SE9' color='structure' size='500' frame='true' align='right' caption='ToxT complex with palmitoleic acid, 1.9 Angstrom resolution crystal structure, [[3gbg]]' >


Retrieved from "https://proteopedia.org/VRC01_gp120_complex"