1fyt

From Proteopedia

(Difference between revisions)

Current revision

CRYSTAL STRUCTURE OF A COMPLEX OF A HUMAN ALPHA/BETA-T CELL RECEPTOR, INFLUENZA HA ANTIGEN PEPTIDE, AND MHC CLASS II MOLECULE, HLA-DR1

Structural highlights

1fyt is a 5 chain structure with sequence from H3N2 subtype and Homo sapiens. The March 2005 RCSB PDB Molecule of the Month feature on T-Cell Receptor by David S. Goodsell is 10.2210/rcsb_pdb/mom_2005_3. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DRA_HUMAN Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

An alphabeta T-cell receptor (alphabetaTCR)/hemagglutinin (HA) peptide/human leukocyte antigen (HLA)-DR1 complex was stabilized by flexibly linking the HA peptide with the human HA1.7 alphabetaTCR, to increase the local concentration of the interacting proteins once the peptide has been loaded onto the major histocompatibility complex (MHC) molecule. The structure of the complex, determined by X-ray crystallography, has a binding mode similar to that of the human B7 alphabetaTCR on a pMHCI molecule. Twelve of the 15 MHC residues contacted are at the same positions observed earlier in class I MHC/peptide/TCR complexes. One contact, to an MHC loop outside the peptide-binding site, is conserved and specific to pMHCII complexes. TCR gene usage in the response to HA/HLA-DR appears to conserve charged interactions between three lysines of the peptide and acidic residues on the TCR.

Structure of a covalently stabilized complex of a human alphabeta T-cell receptor, influenza HA peptide and MHC class II molecule, HLA-DR1.,Hennecke J, Carfi A, Wiley DC EMBO J. 2000 Nov 1;19(21):5611-24. PMID:11060013^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hennecke J, Carfi A, Wiley DC. Structure of a covalently stabilized complex of a human alphabeta T-cell receptor, influenza HA peptide and MHC class II molecule, HLA-DR1. EMBO J. 2000 Nov 1;19(21):5611-24. PMID:11060013 doi:10.1093/emboj/19.21.5611

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1fyt"

@@ Line 15: / Line 15: @@
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fy/1fyt_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
 </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1fyt ConSurf].
 <div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+An alphabeta T-cell receptor (alphabetaTCR)/hemagglutinin (HA) peptide/human leukocyte antigen (HLA)-DR1 complex was stabilized by flexibly linking the HA peptide with the human HA1.7 alphabetaTCR, to increase the local concentration of the interacting proteins once the peptide has been loaded onto the major histocompatibility complex (MHC) molecule. The structure of the complex, determined by X-ray crystallography, has a binding mode similar to that of the human B7 alphabetaTCR on a pMHCI molecule. Twelve of the 15 MHC residues contacted are at the same positions observed earlier in class I MHC/peptide/TCR complexes. One contact, to an MHC loop outside the peptide-binding site, is conserved and specific to pMHCII complexes. TCR gene usage in the response to HA/HLA-DR appears to conserve charged interactions between three lysines of the peptide and acidic residues on the TCR.
+Structure of a covalently stabilized complex of a human alphabeta T-cell receptor, influenza HA peptide and MHC class II molecule, HLA-DR1.,Hennecke J, Carfi A, Wiley DC EMBO J. 2000 Nov 1;19(21):5611-24. PMID:11060013<ref>PMID:11060013</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1fyt" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 25: / Line 34: @@
 *[[MHC II 3D structures|MHC II 3D structures]]
 *[[T-cell receptor 3D structures|T-cell receptor 3D structures]]
+== References ==
+<references/>
 __TOC__
 </StructureSection>

1fyt

From Proteopedia

Current revision

CRYSTAL STRUCTURE OF A COMPLEX OF A HUMAN ALPHA/BETA-T CELL RECEPTOR, INFLUENZA HA ANTIGEN PEPTIDE, AND MHC CLASS II MOLECULE, HLA-DR1

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox