1ndg: Difference between revisions

Revision as of 15:04, 21 February 2008

Crystal structure of Fab fragment of antibody HyHEL-8 complexed with its antigen lysozyme

OverviewOverview

The process whereby the immune system generates antibodies of higher affinities during a response to antigen (affinity maturation) is a prototypical example of molecular evolution. Earlier studies have been confined to antibodies specific for small molecules (haptens) rather than for proteins. We compare the structures of four antibodies bound to the same site on hen egg white lysozyme (HEL) at different stages of affinity maturation. These X-ray snapshots reveal that binding is enhanced, not through the formation of additional hydrogen bonds or van der Waals contacts or by an increase in total buried surface, but by burial of increasing amounts of apolar surface at the expense of polar surface, accompanied by improved shape complementarity. The increase in hydrophobic interactions results from highly correlated rearrangements in antibody residues at the interface periphery, adjacent to the central energetic hot spot. This first visualization of the maturation of antibodies to protein provides insights into the evolution of high affinity in other protein-protein interfaces.

About this StructureAbout this Structure

1NDG is a Protein complex structure of sequences from Gallus gallus and Mus musculus with as ligand. Active as Lysozyme, with EC number 3.2.1.17 Full crystallographic information is available from OCA.

ReferenceReference

X-ray snapshots of the maturation of an antibody response to a protein antigen., Li Y, Li H, Yang F, Smith-Gill SJ, Mariuzza RA, Nat Struct Biol. 2003 Jun;10(6):482-8. PMID:12740607

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 ==Overview==
-The process whereby the immune system generates antibodies of higher, affinities during a response to antigen (affinity maturation) is a, prototypical example of molecular evolution. Earlier studies have been, confined to antibodies specific for small molecules (haptens) rather than, for proteins. We compare the structures of four antibodies bound to the, same site on hen egg white lysozyme (HEL) at different stages of affinity, maturation. These X-ray snapshots reveal that binding is enhanced, not, through the formation of additional hydrogen bonds or van der Waals, contacts or by an increase in total buried surface, but by burial of, increasing amounts of apolar surface at the expense of polar surface, accompanied by improved shape complementarity. The increase in hydrophobic, interactions results from highly correlated rearrangements in antibody, residues at the interface periphery, adjacent to the central energetic hot, spot. This first visualization of the maturation of antibodies to protein, provides insights into the evolution of high affinity in other, protein-protein interfaces.
+The process whereby the immune system generates antibodies of higher affinities during a response to antigen (affinity maturation) is a prototypical example of molecular evolution. Earlier studies have been confined to antibodies specific for small molecules (haptens) rather than for proteins. We compare the structures of four antibodies bound to the same site on hen egg white lysozyme (HEL) at different stages of affinity maturation. These X-ray snapshots reveal that binding is enhanced, not through the formation of additional hydrogen bonds or van der Waals contacts or by an increase in total buried surface, but by burial of increasing amounts of apolar surface at the expense of polar surface, accompanied by improved shape complementarity. The increase in hydrophobic interactions results from highly correlated rearrangements in antibody residues at the interface periphery, adjacent to the central energetic hot spot. This first visualization of the maturation of antibodies to protein provides insights into the evolution of high affinity in other protein-protein interfaces.
 ==About this Structure==
@@ Line 17: / Line 17: @@
 [[Category: Li, H.]]
 [[Category: Li, Y.]]
-[[Category: Mariuzza, R.A.]]
+[[Category: Mariuzza, R A.]]
-[[Category: Smith-Gill, S.J.]]
+[[Category: Smith-Gill, S J.]]
 [[Category: Yang, F.]]
 [[Category: ACY]]
 [[Category: antibody; lysozyme; mutant; hyhel-8]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:28:38 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:04:54 2008''