Transcript Re evaluating the Categorization of HIV Progression in Subjects

Residue Sequence and Structure in
the Re evaluation the Categorization
of HIV Progression in Subjects Based
on CD4 T cell Decline Rates
Angela Garibaldi & Ryan Willhite
Loyola Marymount University
BIOL 398-01
March 23, 2010
Outline
• Review of previous experiment using CD4
decline rates
• Structure based hypothesis
• Methods and programs used
• Results
• Comparison to More Recent Studies
• References
Recap of past experiment
• Evaluated the categorization of progressors
based on CD4 decline rates
• Analyzed two moderate progressors (6,7) with
rates comparable to non-progressor 13 and
rapid progressor 10.
• Based on divergence and diversity subject 6
did not act as non-progressor
• Subject 7 acted like a rapid progressor.
Hypothesis
• Subject 7 will be more similar to
Methods
• Create phylogenetic trees based on amino
acid sequence
• Use ProtPram to analyze residue composition
in subjects 6,7,5,10
• Select 7 and 10 for time point analysis
– First clone for selected visits used
• Use Cn3d to analyze differences in 3d
structure
Phylogenetics based on amino acid
sequence
10 vs 5
10 vs 7
5 vs 7
Subject 6 v 13
Subjects 6 v 7
Subjects 13 v 5
Subjects 6 v 5
Overall residue composition
•All clones available were used in this analysis per
individual
•Rapid Progressor Subject 10 is the only one with Asn
as its most prevalent residue
ProtParam
Physico-chemical properties of a
protein using ExPASy server
Subject 5 Properties
Subject 6
Subject 7
Subject 10
Residue composition over time
Residue composition over time
• All clones from selected visits were used.
• Subject 10, Rapid Progressor shows Asn as its
prevalent residue over time.
• Subject 7, Moderate Progressor begins with Asn as
prevalent residue
• Subject 10 showed sudden jump in Arg %. This may
be an artifact.
Conclusion
• The highest percent of amino acids found in the
moderates 5,6, and 7 is (Ile)
• The highest percent of amino acids found in the rapid
10 to compare is (Asn)
• Looking at these compositions along with protein
structure seems to be a more efficient way of
categorizing progression
• The difference in amino acid composition suggests a
role in type of progression
A more recent study
• Structure of HIV-1 gp120 with gp41interactive region reveals layered envelope
architecture and basis of conformational
mobility
gp120, gp41-interactive region
structure
•7-stranded β-sandwich,invariant in conformation
•highly glycosylated gp120
outer domain. layers act as a
shape-changing spacer,
facilitating movement
between outer domain and
gp41-associated β-sandwich
• provide for conformational
diversity used in immune
evasion.
• A “layered” gp120
References
• Structure of HIV-1 gp120 with gp41interactive region reveals layered envelope
architecture and basis of conformational
mobility