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1q68

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Revision as of 07:44, 9 December 2020

Solution structure of T-cell surface glycoprotein CD4 and Proto-oncogene tyrosine-protein kinase LCK fragments

Structural highlights

1q68 is a 2 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	CD4 (HUMAN), LCK (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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.

Function

[CD4_HUMAN] Accessory protein for MHC class-II antigen/T-cell receptor interaction. May regulate T-cell activation. Induces the aggregation of lipid rafts. [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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

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

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^[7]

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

References

↑ Gelkop S, Gish GD, Babichev Y, Pawson T, Isakov N. T cell activation-induced CrkII binding to the Zap70 protein tyrosine kinase is mediated by Lck-dependent phosphorylation of Zap70 tyrosine 315. J Immunol. 2005 Dec 15;175(12):8123-32. PMID:16339550
↑ Mason LH, Willette-Brown J, Taylor LS, McVicar DW. Regulation of Ly49D/DAP12 signal transduction by Src-family kinases and CD45. J Immunol. 2006 Jun 1;176(11):6615-23. PMID:16709819
↑ Goh YM, Cinghu S, Hong ET, Lee YS, Kim JH, Jang JW, Li YH, Chi XZ, Lee KS, Wee H, Ito Y, Oh BC, Bae SC. Src kinase phosphorylates RUNX3 at tyrosine residues and localizes the protein in the cytoplasm. J Biol Chem. 2010 Mar 26;285(13):10122-9. doi: 10.1074/jbc.M109.071381. Epub 2010, Jan 25. PMID:20100835 doi:10.1074/jbc.M109.071381
↑ Collins M, Tremblay M, Chapman N, Curtiss M, Rothman PB, Houtman JC. The T cell receptor-mediated phosphorylation of Pyk2 tyrosines 402 and 580 occurs via a distinct mechanism than other receptor systems. J Leukoc Biol. 2009 Dec 22. PMID:20028775 doi:jlb.0409227
↑ Wang H, Zeng X, Fan Z, Lim B. RhoH modulates pre-TCR and TCR signalling by regulating LCK. Cell Signal. 2011 Jan;23(1):249-58. doi: 10.1016/j.cellsig.2010.09.009. Epub 2010, Sep 16. PMID:20851766 doi:10.1016/j.cellsig.2010.09.009
↑ Scales TM, Derkinderen P, Leung KY, Byers HL, Ward MA, Price C, Bird IN, Perera T, Kellie S, Williamson R, Anderton BH, Reynolds CH. Tyrosine phosphorylation of tau by the SRC family kinases lck and fyn. Mol Neurodegener. 2011 Jan 26;6:12. doi: 10.1186/1750-1326-6-12. PMID:21269457 doi:10.1186/1750-1326-6-12
↑ 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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1q68"

@@ Line 1: / Line 1: @@
 ==Solution structure of T-cell surface glycoprotein CD4 and Proto-oncogene tyrosine-protein kinase LCK fragments==
-<StructureSection load='1q68' size='340' side='right' caption='[[1q68]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
+<StructureSection load='1q68' size='340' side='right'caption='[[1q68]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1q68]] 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=1Q68 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Q68 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1q68]] 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=1Q68 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1Q68 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD4 ([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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1q68 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q68 OCA], [http://pdbe.org/1q68 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1q68 RCSB], [http://www.ebi.ac.uk/pdbsum/1q68 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1q68 ProSAT]</span></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=1q68 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q68 OCA], [http://pdbe.org/1q68 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1q68 RCSB], [http://www.ebi.ac.uk/pdbsum/1q68 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1q68 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 33: / Line 33: @@
 ==See Also==
-*[[CD4|CD4]]
+*[[CD4 3D structures|CD4 3D structures]]
+*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
 == References ==
 <references/>
@@ Line 39: / Line 40: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Blacklow, S C]]
 [[Category: Eck, M J]]

1q68

From Proteopedia

Revision as of 07:44, 9 December 2020

Solution structure of T-cell surface glycoprotein CD4 and Proto-oncogene tyrosine-protein kinase LCK fragments

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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