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==Solution structure of T-cell surface glycoprotein CD8 alpha chain and Proto-oncogene tyrosine-protein kinase LCK fragments==
==Solution structure of T-cell surface glycoprotein CD8 alpha chain and Proto-oncogene tyrosine-protein kinase LCK fragments==
<StructureSection load='1q69' size='340' side='right'caption='[[1q69]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
<StructureSection load='1q69' size='340' side='right'caption='[[1q69]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1q69]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q69 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1Q69 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1q69]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q69 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD8A OR MAL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), LCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1q69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q69 OCA], [http://pdbe.org/1q69 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1q69 RCSB], [http://www.ebi.ac.uk/pdbsum/1q69 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1q69 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1q69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q69 OCA], [https://pdbe.org/1q69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q69 RCSB], [https://www.ebi.ac.uk/pdbsum/1q69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q69 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/CD8A_HUMAN CD8A_HUMAN]] Defects in CD8A are a cause of familial CD8 deficiency (CD8 deficiency) [MIM:[http://omim.org/entry/608957 608957]]. Familial CD8 deficiency is a novel autosomal recessive immunologic defect characterized by absence of CD8+ cells, leading to recurrent bacterial infections. [[http://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Severe combined immunodeficiency due to LCK deficiency. Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.  
[https://www.uniprot.org/uniprot/CD8A_HUMAN CD8A_HUMAN] Defects in CD8A are a cause of familial CD8 deficiency (CD8 deficiency) [MIM:[https://omim.org/entry/608957 608957]. Familial CD8 deficiency is a novel autosomal recessive immunologic defect characterized by absence of CD8+ cells, leading to recurrent bacterial infections.
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/CD8A_HUMAN CD8A_HUMAN]] Identifies cytotoxic/suppressor T-cells that interact with MHC class I bearing targets. CD8 is thought to play a role in the process of T-cell mediated killing. CD8 alpha chains binds to class I MHC molecules alpha-3 domains. [[http://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP.<ref>PMID:16339550</ref> <ref>PMID:16709819</ref> <ref>PMID:20100835</ref> <ref>PMID:20028775</ref> <ref>PMID:20851766</ref> <ref>PMID:21269457</ref> 
[https://www.uniprot.org/uniprot/CD8A_HUMAN CD8A_HUMAN] Identifies cytotoxic/suppressor T-cells that interact with MHC class I bearing targets. CD8 is thought to play a role in the process of T-cell mediated killing. CD8 alpha chains binds to class I MHC molecules alpha-3 domains.
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Blacklow, S C]]
[[Category: Blacklow SC]]
[[Category: Eck, M J]]
[[Category: Eck MJ]]
[[Category: Kim, P W]]
[[Category: Kim PW]]
[[Category: Sun, Z Y]]
[[Category: Sun ZY]]
[[Category: Wagner, G]]
[[Category: Wagner G]]
[[Category: Beta hairpin]]
[[Category: Helix-helix interaction]]
[[Category: Membrane protein-transferase complex]]
[[Category: Peptide-peptide complex]]
[[Category: Zinc coordination]]

Latest revision as of 14:24, 2 August 2023

Solution structure of T-cell surface glycoprotein CD8 alpha chain and Proto-oncogene tyrosine-protein kinase LCK fragmentsSolution structure of T-cell surface glycoprotein CD8 alpha chain and Proto-oncogene tyrosine-protein kinase LCK fragments

Structural highlights

1q69 is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CD8A_HUMAN Defects in CD8A are a cause of familial CD8 deficiency (CD8 deficiency) [MIM:608957. Familial CD8 deficiency is a novel autosomal recessive immunologic defect characterized by absence of CD8+ cells, leading to recurrent bacterial infections.

Function

CD8A_HUMAN Identifies cytotoxic/suppressor T-cells that interact with MHC class I bearing targets. CD8 is thought to play a role in the process of T-cell mediated killing. CD8 alpha chains binds to class I MHC molecules alpha-3 domains.

Publication Abstract from PubMed

The T cell coreceptors CD4 and CD8 both associate via their cytoplasmic tails with the N-terminus of the Src-family tyrosine kinase Lck. These interactions require zinc and are critical for T cell development and activation. We examined the folding and solution structures of ternary CD4-Lck-Zn2+ and CD8alpha-Lck-Zn2+ complexes. The coreceptor tails and the Lck N-terminus are unstructured in isolation but assemble in the presence of zinc to form compactly folded heterodimeric domains. The cofolded complexes have similar "zinc clasp" cores that are augmented by distinct structural elements. A dileucine motif required for clathrin-mediated endocytosis of CD4 is masked by Lck.

A zinc clasp structure tethers Lck to T cell coreceptors CD4 and CD8.,Kim PW, Sun ZY, Blacklow SC, Wagner G, Eck MJ Science. 2003 Sep 19;301(5640):1725-8. PMID:14500983[1]

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

See Also

References

  1. ↑ Kim PW, Sun ZY, Blacklow SC, Wagner G, Eck MJ. A zinc clasp structure tethers Lck to T cell coreceptors CD4 and CD8. Science. 2003 Sep 19;301(5640):1725-8. PMID:14500983 doi:10.1126/science.1085643
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