1fng: Difference between revisions

Revision as of 13:40, 21 February 2008

HISTOCOMPATIBILITY ANTIGEN

OverviewOverview

To better understand TCR discrimination of multiple ligands, we have analyzed the crystal structures of two Hb peptide/I-E(k) complexes that differ by only a single amino acid substitution at the P6 anchor position within the peptide (E73D). Detailed comparison of multiple independently determined structures at 1.9 A resolution reveals that removal of a single buried methylene group can alter a critical portion of the TCR recognition surface. Significant variance was observed in the peptide P5-P8 main chain as well as a rotamer difference at LeuP8, approximately 10 A distal from the substitution. No significant variations were observed in the conformation of the two MHC class II molecules. The ligand alteration results in two peptide/MHC complexes that generate bulk T cell responses that are distinct and essentially nonoverlapping. For the Hb-specific T cell 3.L2, substitution reduces the potency of the ligand 1000-fold. Soluble 3.L2 TCR binds the two peptide/MHC complexes with similar affinity, although with faster kinetics. These results highlight the role of subtle variations in MHC Ag presentation on T cell activation and signaling.

About this StructureAbout this Structure

1FNG is a Protein complex structure of sequences from Mus musculus with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

Structural and functional consequences of altering a peptide MHC anchor residue., Kersh GJ, Miley MJ, Nelson CA, Grakoui A, Horvath S, Donermeyer DL, Kappler J, Allen PM, Fremont DH, J Immunol. 2001 Mar 1;166(5):3345-54. PMID:11207290

Page seeded by OCA on Thu Feb 21 12:40:31 2008

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

OCA

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-[[Image:1fng.gif|left|200px]]<br /><applet load="1fng" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1fng.gif|left|200px]]<br /><applet load="1fng" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1fng, resolution 1.90&Aring;" />
 '''HISTOCOMPATIBILITY ANTIGEN'''<br />
 ==Overview==
-To better understand TCR discrimination of multiple ligands, we have, analyzed the crystal structures of two Hb peptide/I-E(k) complexes that, differ by only a single amino acid substitution at the P6 anchor position, within the peptide (E73D). Detailed comparison of multiple independently, determined structures at 1.9 A resolution reveals that removal of a single, buried methylene group can alter a critical portion of the TCR recognition, surface. Significant variance was observed in the peptide P5-P8 main chain, as well as a rotamer difference at LeuP8, approximately 10 A distal from, the substitution. No significant variations were observed in the, conformation of the two MHC class II molecules. The ligand alteration, results in two peptide/MHC complexes that generate bulk T cell responses, that are distinct and essentially nonoverlapping. For the Hb-specific T, cell 3.L2, substitution reduces the potency of the ligand 1000-fold., Soluble 3.L2 TCR binds the two peptide/MHC complexes with similar, affinity, although with faster kinetics. These results highlight the role, of subtle variations in MHC Ag presentation on T cell activation and, signaling.
+To better understand TCR discrimination of multiple ligands, we have analyzed the crystal structures of two Hb peptide/I-E(k) complexes that differ by only a single amino acid substitution at the P6 anchor position within the peptide (E73D). Detailed comparison of multiple independently determined structures at 1.9 A resolution reveals that removal of a single buried methylene group can alter a critical portion of the TCR recognition surface. Significant variance was observed in the peptide P5-P8 main chain as well as a rotamer difference at LeuP8, approximately 10 A distal from the substitution. No significant variations were observed in the conformation of the two MHC class II molecules. The ligand alteration results in two peptide/MHC complexes that generate bulk T cell responses that are distinct and essentially nonoverlapping. For the Hb-specific T cell 3.L2, substitution reduces the potency of the ligand 1000-fold. Soluble 3.L2 TCR binds the two peptide/MHC complexes with similar affinity, although with faster kinetics. These results highlight the role of subtle variations in MHC Ag presentation on T cell activation and signaling.
 ==About this Structure==
-FNG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with NAG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FNG OCA].
+FNG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=NAG:'>NAG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FNG OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Mus musculus]]
 [[Category: Protein complex]]
-[[Category: Fremont, D.H.]]
+[[Category: Fremont, D H.]]
-[[Category: Miley, M.J.]]
+[[Category: Miley, M J.]]
-[[Category: Nelson, C.A.]]
+[[Category: Nelson, C A.]]
 [[Category: NAG]]
 [[Category: histocompatibility antigen]]
@@ Line 22: / Line 22: @@
 [[Category: peptide]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 15:03:55 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:40:31 2008''