2G12 Structure*
Compared to Ordinary Fab Structure
Intact IgG
Ordinary Fab
Two adjacent Fab's
Morph: 2 Fab's -> 2G12
Backbones
(
slower
)
Spacefilled
(
slower
)
(If the morph window is too small, resize it, then refresh/reload.)
2G12 Framework Somatic Hypermutation Details
(1op5 3.0 Å: 1
o
ligand 400 Å
2
, 2
o
300 Å
2
. 8-9 HBonds in each.)
A.
Framework mutations for 1OP3
(two disaccharide contacts)
B.
Crystal contacts showing oligosaccharide contacts
1om3
(unliganded 2.2 Å)
1op3
(w/ disaccharide 1.75 Å)
Proposed gp120 epitope
gp120 has 25 N-linked glycosylation sites.
"The gp120 crystallized was from the HXBc2 strain of HIV-1. It has deletions of 52 and 19 residues from the N and C termini, respectively; Gly-Ala-Gly tripeptide substitutions for 67 V1/V2 loop residues and 32 V3 loop residues; and the
removal of all sugar groups beyond the linkages between the two core N-acetylglucosamine residues
. This deglycosylated core gp120 is
stripped of over 90% of the carbohydrate
but it retains over 80% of the non-variable-loop protein. Its capacity to interact with CD4 and relevant antibodies is preserved at or near wild-type levels." (
Kwong PD,
et al., Nature
393:648 (1998)
)
* A presentation in Protein Explorer by Eric Martz to illustrate a talk on "Antibody domain exchange is an immunological solution to carbohydrate cluster recognition" (
Calarese
et al., Science
30:2065, 2003
).