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| | ==Structures and Interaction Analyses of the Integrin Alpha-M Beta-2 Cytoplasmic Tails== | | ==Structures and Interaction Analyses of the Integrin Alpha-M Beta-2 Cytoplasmic Tails== |
| - | <StructureSection load='2lkj' size='340' side='right'caption='[[2lkj]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2lkj' size='340' side='right'caption='[[2lkj]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2lkj]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LKJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LKJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2lkj]] is a 1 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=2LKJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LKJ FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2lke|2lke]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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=2lkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lkj OCA], [https://pdbe.org/2lkj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lkj RCSB], [https://www.ebi.ac.uk/pdbsum/2lkj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lkj 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=2lkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lkj OCA], [https://pdbe.org/2lkj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lkj RCSB], [https://www.ebi.ac.uk/pdbsum/2lkj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lkj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/ITAM_HUMAN ITAM_HUMAN]] Genetic variations in ITGAM has been associated with susceptibility to systemic lupus erythematosus type 6 (SLEB6) [MIM:[https://omim.org/entry/609939 609939]]. Systemic lupus erythematosus (SLE) is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system.
| + | [https://www.uniprot.org/uniprot/ITAM_HUMAN ITAM_HUMAN] Genetic variations in ITGAM has been associated with susceptibility to systemic lupus erythematosus type 6 (SLEB6) [MIM:[https://omim.org/entry/609939 609939]. Systemic lupus erythematosus (SLE) is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ITAM_HUMAN ITAM_HUMAN]] Integrin alpha-M/beta-2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles. It is identical with CR-3, the receptor for the iC3b fragment of the third complement component. It probably recognizes the R-G-D peptide in C3b. Integrin alpha-M/beta-2 is also a receptor for fibrinogen, factor X and ICAM1. It recognizes P1 and P2 peptides of fibrinogen gamma chain.
| + | [https://www.uniprot.org/uniprot/ITAM_HUMAN ITAM_HUMAN] Integrin alpha-M/beta-2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles. It is identical with CR-3, the receptor for the iC3b fragment of the third complement component. It probably recognizes the R-G-D peptide in C3b. Integrin alpha-M/beta-2 is also a receptor for fibrinogen, factor X and ICAM1. It recognizes P1 and P2 peptides of fibrinogen gamma chain. |
| | <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: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Amalraj, M]] | + | [[Category: Amalraj M]] |
| - | [[Category: Bhattacharjya, S]] | + | [[Category: Bhattacharjya S]] |
| - | [[Category: Chua, G L]] | + | [[Category: Chua GL]] |
| - | [[Category: Tan, S M]] | + | [[Category: Tan SM]] |
| - | [[Category: Tang, X Y]] | + | [[Category: Tang XY]] |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: Cytoplasmic]]
| + | |
| - | [[Category: Dpc micelle]]
| + | |
| - | [[Category: Mac-1 alpha]]
| + | |
| - | [[Category: Myristoylated]]
| + | |
| - | [[Category: Serine phosphorylated]]
| + | |
| Structural highlights
Disease
ITAM_HUMAN Genetic variations in ITGAM has been associated with susceptibility to systemic lupus erythematosus type 6 (SLEB6) [MIM:609939. Systemic lupus erythematosus (SLE) is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system.
Function
ITAM_HUMAN Integrin alpha-M/beta-2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles. It is identical with CR-3, the receptor for the iC3b fragment of the third complement component. It probably recognizes the R-G-D peptide in C3b. Integrin alpha-M/beta-2 is also a receptor for fibrinogen, factor X and ICAM1. It recognizes P1 and P2 peptides of fibrinogen gamma chain.
Publication Abstract from PubMed
Integrins are hetero-dimeric (alpha and beta subunits) signal transducer proteins involved in cell adhesions and migrations. The cytosolic tails of integrins are essential for transmitting bi-directional signaling and also implicated in maintaining the resting states of the receptors. In addition, cytosolic tails of integrin often undergo post-translation modification like phosphorylation. However, consequences of phosphorylation on the structures and interactions are not clear. The leukocyte-specific integrin alphaMbeta2 is essential for myeloid cell adhesion, phagocytosis and degranulation. In this work, we determine solution structures of myristoylated cytosolic tail of alphaM and a Ser phosphorylated variant in DPC micelles by NMR spectroscopy. Further, the interactions between alphaM tails, non phosphorylated and phosphorylated, with beta2 tail are investigated by NMR and fluorescence resonance energy transfer (FRET). The 3D structures of the 24-residue cytosolic tail of alphaM or phosphorylated alphaM are characterized by an N-terminal amphipathic helix and a loop at the C-terminus. The residues at the loop contain packing interactions with the hydrophobic face of the helix. 15N-1H HSQC experiments identify residues of alphaM and beta2 tails, those may be involved in formation of tail-tail hetero-complex. We have further examined interactions between myristoylated beta2 tail, in DPC micelles, with dansylated alphaM tail peptides by FRET. These studies reveal enhanced interactions between alphaM or phosphorylated alphaM tails with beta2 tail with Kd ~ 5.2+0.6 alphaM and Kd ~4.4+0.7 alphaM, respectively. Docked structures of tail/tail complexes delineated that alphaM/beta2 interface at the cytosolic region could be sustained by a network of polar interactions, ionic and/or hydrogen bonds.
Structures and interaction analyses of the integrin alphaMbeta2 cytoplasmic tails.,Chua GL, Tang XY, Amalraj M, Tan SM, Bhattacharjya S J Biol Chem. 2011 Nov 3. PMID:22052909[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chua GL, Tang XY, Amalraj M, Tan SM, Bhattacharjya S. Structures and interaction analyses of the integrin alphaMbeta2 cytoplasmic tails. J Biol Chem. 2011 Nov 3. PMID:22052909 doi:10.1074/jbc.M111.280164
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