1frg: Difference between revisions

Revision as of 13:41, 21 February 2008

CRYSTAL STRUCTURE, SEQUENCE, AND EPITOPE MAPPING OF A PEPTIDE COMPLEX OF AN ANTI-INFLUENZA HA PEPTIDE ANTIBODY FAB 26(SLASH)9: FINE-TUNING ANTIBODY SPECIFICITY

OverviewOverview

The three-dimensional structure of the complex of a second anti-peptide antibody (Fab 26/9) that recognizes the same six-residue epitope of an immunogenic peptide from influenza virus hemagglutinin (HA1; 75-110) as Fab 17/9 with the peptide has been determined at 2.8 A resolution. The amino acid sequence of the variable region of the 26/9 antibody differs in 24 positions from that of 17/9, the first antibody in this series for which several ligand-bound and free structures have been determined and refined. Comparison of the 26/9-peptide with the 17/9-peptide complex structures shows that the two Fabs are very similar (r.m.s.d. 0.5 to 0.8 A) and that the peptide antigen (101-107) has virtually the same conformation (r.m.s.d. 0.3 to 0.8 A) when bound to both antibodies. A sequence difference in the 26/9 binding pocket (L94; His in 26/9, Asn in 17/9) results in an interaction with a bound water molecule that is not seen in the 17/9 structures. Epitope mapping shows that the relative specificity of 26/9 and 17/9 antibodies for individual positions of the peptide antigen are slightly different. Amino acid substitutions in the peptide, particularly at position SerP107, are tolerated to different extents by 17/9 and 26/9. Structural and sequence analysis suggests that amino acid differences near the peptide-binding site are responsible for altering slightly the specificity of 26/9 for three peptide residues and illustrates how amino acid substitutions can modify antibody-antigen interactions and thereby modulate antibody specificity.

About this StructureAbout this Structure

1FRG is a Protein complex structure of sequences from [1] with and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of a peptide complex of anti-influenza peptide antibody Fab 26/9. Comparison of two different antibodies bound to the same peptide antigen., Churchill ME, Stura EA, Pinilla C, Appel JR, Houghten RA, Kono DH, Balderas RS, Fieser GG, Schulze-Gahmen U, Wilson IA, J Mol Biol. 1994 Aug 26;241(4):534-56. PMID:7520084

Page seeded by OCA on Thu Feb 21 12:41:52 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1frg.gif|left|200px]]<br />
+[[Image:1frg.gif|left|200px]]<br /><applet load="1frg" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1frg" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1frg, resolution 2.8&Aring;" />
 '''CRYSTAL STRUCTURE, SEQUENCE, AND EPITOPE MAPPING OF A PEPTIDE COMPLEX OF AN ANTI-INFLUENZA HA PEPTIDE ANTIBODY FAB 26(SLASH)9: FINE-TUNING ANTIBODY SPECIFICITY'''<br />
 ==Overview==
-The three-dimensional structure of the complex of a second anti-peptide, antibody (Fab 26/9) that recognizes the same six-residue epitope of an, immunogenic peptide from influenza virus hemagglutinin (HA1; 75-110) as, Fab 17/9 with the peptide has been determined at 2.8 A resolution. The, amino acid sequence of the variable region of the 26/9 antibody differs in, 24 positions from that of 17/9, the first antibody in this series for, which several ligand-bound and free structures have been determined and, refined. Comparison of the 26/9-peptide with the 17/9-peptide complex, structures shows that the two Fabs are very similar (r.m.s.d. 0.5 to 0.8, A) and that the peptide antigen (101-107) has virtually the same, conformation (r.m.s.d. 0.3 to 0.8 A) when bound to both antibodies. A, sequence difference in the 26/9 binding pocket (L94; His in 26/9, Asn in, 17/9) results in an interaction with a bound water molecule that is not, seen in the 17/9 structures. Epitope mapping shows that the relative, specificity of 26/9 and 17/9 antibodies for individual positions of the, peptide antigen are slightly different. Amino acid substitutions in the, peptide, particularly at position SerP107, are tolerated to different, extents by 17/9 and 26/9. Structural and sequence analysis suggests that, amino acid differences near the peptide-binding site are responsible for, altering slightly the specificity of 26/9 for three peptide residues and, illustrates how amino acid substitutions can modify antibody-antigen, interactions and thereby modulate antibody specificity.
+The three-dimensional structure of the complex of a second anti-peptide antibody (Fab 26/9) that recognizes the same six-residue epitope of an immunogenic peptide from influenza virus hemagglutinin (HA1; 75-110) as Fab 17/9 with the peptide has been determined at 2.8 A resolution. The amino acid sequence of the variable region of the 26/9 antibody differs in 24 positions from that of 17/9, the first antibody in this series for which several ligand-bound and free structures have been determined and refined. Comparison of the 26/9-peptide with the 17/9-peptide complex structures shows that the two Fabs are very similar (r.m.s.d. 0.5 to 0.8 A) and that the peptide antigen (101-107) has virtually the same conformation (r.m.s.d. 0.3 to 0.8 A) when bound to both antibodies. A sequence difference in the 26/9 binding pocket (L94; His in 26/9, Asn in 17/9) results in an interaction with a bound water molecule that is not seen in the 17/9 structures. Epitope mapping shows that the relative specificity of 26/9 and 17/9 antibodies for individual positions of the peptide antigen are slightly different. Amino acid substitutions in the peptide, particularly at position SerP107, are tolerated to different extents by 17/9 and 26/9. Structural and sequence analysis suggests that amino acid differences near the peptide-binding site are responsible for altering slightly the specificity of 26/9 for three peptide residues and illustrates how amino acid substitutions can modify antibody-antigen interactions and thereby modulate antibody specificity.
 ==About this Structure==
-FRG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with ACE and NH2 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FRG OCA].
+FRG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=ACE:'>ACE</scene> and <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FRG OCA].
 ==Reference==
 Crystal structure of a peptide complex of anti-influenza peptide antibody Fab 26/9. Comparison of two different antibodies bound to the same peptide antigen., Churchill ME, Stura EA, Pinilla C, Appel JR, Houghten RA, Kono DH, Balderas RS, Fieser GG, Schulze-Gahmen U, Wilson IA, J Mol Biol. 1994 Aug 26;241(4):534-56. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7520084 7520084]
 [[Category: Protein complex]]
-[[Category: Churchill, M.E.A.]]
+[[Category: Churchill, M E.A.]]
-[[Category: Wilson, I.A.]]
+[[Category: Wilson, I A.]]
 [[Category: ACE]]
 [[Category: NH2]]
 [[Category: immunoglobulin/virus hemagglutinin]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 18 09:30:37 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:41:52 2008''