J'aime C. Moehlman's Week 7
From OpenWetWare
Terms and Definitions
- Syncytia:
- Fab fragments:
- X-ray Crystallography:
- Tropism:
- Ternary (complex):
- Ramachandran:
- Isomorphously:
Article Outline
Dual conformations for the HIV-1 gp120 V3 loop in complexes with different neutralizing Fabs
- Stanfield et al. (1999)
Introduction
- HIV-1 is a member of the lentivirus subfamily of retroviruses.
- Beta- chemokine receptors have been implicated as the viral secondary receptors.
- CXCR4 acrs as the primary receptor for T cell tropic SI isolates.
- The V3 region is a disulfide look of about 40 amino acids.
- The V3 region is one of the major immunogenic sites.
- Exposure of the V3 loop to the gp120 protein varies depending on the viral isolate type and increases during interactions with CD4.
- Sequence changes in V3 can alter ciral cell tropism, antibody neutralization, neutralization of soluble CD4, syncytium formation, and chemokine receptor usage.
- T- tropic V3 sequences are usually more basic in charge than M-tropic sequences through accumulation of positively charged residues.
- Some amino acid positions in the loop are highly variable in amino acid composition.
- Their investigation was conducted by studying neutralizing antibodies and their complexes with V3 peptides to determine the tertiary conformation of the V3 loop.
- The researchers believe that they can explain coreceptor usage and the changes that take place in the virus upon conversion from a primary M-tropic isolate to the T-tropic strains associated with disease progression.
- Fab 50.1 and 59.1 are the two key structures of antibody fab fragments:
- Fab 50.1 is thought to be highly specific for the MN viral strain
- Fab 59.1 is thought to strongly neutralize IIIB and weakly neutralizes MN.
- In the 59.1 peptide complex 10 amino acid residues were visible and five of these residues had structural counterparts in the 50.1 complex.
- The sidechain of the Arg residue is bound in a deep, negatively charged pocket on the antibody surface.
- Torsion angles are discussed throughout their research.
- They used a synthetic hydrogen bond to mimic incorporating a hydrazone bond-- designed to replace CO-HN hydrogen bond.
- The Fab 58.2 crystal structure shows that it is a highly neutralizing antibody that neutralizes both T-tropic and M-tropic viral strains.
====Results and Discussion====
Structure determination and refinement
Structure description and comparisons
Two different V3 conformations
Correlation of structure with function
