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[[Image:1je6.jpg|left|200px]]<br /><applet load="1je6" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1je6, resolution 2.5&Aring;" />
'''Structure of the MHC Class I Homolog MICB'''<br />


==Overview==
==Structure of the MHC Class I Homolog MICB==
MIC-A and MIC-B are distant MHC class I homologs that serve as, stress-inducible Ags on epithelial and epithelially derived cells. They, are ligands for the widely expressed activating immunoreceptor NKG2D. To, define the structural and functional consequences of sequence differences, between MIC-A and MIC-B and between alleles of MIC-A and alleles of MIC-B, we determined the crystal structure of one allele of human MIC-B., Comparisons between the two previously reported MIC-A crystal structures, and the MIC-B crystal structure show that, as expected, MIC-B is very, similar in structure to MIC-A and likely interacts with NKG2D in an, analogous manner. The interdomain flexibility observed in the MIC-A, structures, a feature unique to MIC proteins among MHC class I proteins, and homologs, is also displayed by MIC-B, with an interdomain relationship, intermediate between the two examples of MIC-A structures. Mapping, sequence variations onto the structures of MIC-A and MIC-B reveals, patterns completely distinct from those displayed by classical MHC class I, proteins, with a number of substitutions falling on positions likely to, affect interactions with NKG2D, but with other positions lying distant, from the NKG2D binding sites or buried within the core of the proteins.
<StructureSection load='1je6' size='340' side='right'caption='[[1je6]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1je6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JE6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JE6 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1je6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1je6 OCA], [https://pdbe.org/1je6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1je6 RCSB], [https://www.ebi.ac.uk/pdbsum/1je6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1je6 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/MICB_HUMAN MICB_HUMAN] Genetic variations in MICA are a cause of susceptibility to rheumatoid arthritis (RA) [MIM:[https://omim.org/entry/180300 180300]. It is a systemic inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Note=The MICB*004 allele is associated with rheumatoid arthritis.  Note=Genetic variation in MICB is associated with cytomegalovirus and herpes simplex virus I seropositivity and this may be associated with schizophrenia risk.
== Function ==
[https://www.uniprot.org/uniprot/MICB_HUMAN MICB_HUMAN] Seems to have no role in antigen presentation. Acts as a stress-induced self-antigen that is recognized by gamma delta T cells. Ligand for the KLRK1/NKG2D receptor. Binding to KLRK1 leads to cell lysis.<ref>PMID:9497295</ref> <ref>PMID:11491531</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/je/1je6_consurf.spt"</scriptWhenChecked>
    <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=1je6 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
MIC-A and MIC-B are distant MHC class I homologs that serve as stress-inducible Ags on epithelial and epithelially derived cells. They are ligands for the widely expressed activating immunoreceptor NKG2D. To define the structural and functional consequences of sequence differences between MIC-A and MIC-B and between alleles of MIC-A and alleles of MIC-B, we determined the crystal structure of one allele of human MIC-B. Comparisons between the two previously reported MIC-A crystal structures and the MIC-B crystal structure show that, as expected, MIC-B is very similar in structure to MIC-A and likely interacts with NKG2D in an analogous manner. The interdomain flexibility observed in the MIC-A structures, a feature unique to MIC proteins among MHC class I proteins and homologs, is also displayed by MIC-B, with an interdomain relationship intermediate between the two examples of MIC-A structures. Mapping sequence variations onto the structures of MIC-A and MIC-B reveals patterns completely distinct from those displayed by classical MHC class I proteins, with a number of substitutions falling on positions likely to affect interactions with NKG2D, but with other positions lying distant from the NKG2D binding sites or buried within the core of the proteins.


==About this Structure==
Structural studies of allelic diversity of the MHC class I homolog MIC-B, a stress-inducible ligand for the activating immunoreceptor NKG2D.,Holmes MA, Li P, Petersdorf EW, Strong RK J Immunol. 2002 Aug 1;169(3):1395-400. PMID:12133964<ref>PMID:12133964</ref>
1JE6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JE6 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Structural studies of allelic diversity of the MHC class I homolog MIC-B, a stress-inducible ligand for the activating immunoreceptor NKG2D., Holmes MA, Li P, Petersdorf EW, Strong RK, J Immunol. 2002 Aug 1;169(3):1395-400. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12133964 12133964]
</div>
<div class="pdbe-citations 1je6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Holmes, M.A.]]
[[Category: Holmes MA]]
[[Category: Li, P.]]
[[Category: Li P]]
[[Category: Strong, R.K.]]
[[Category: Strong RK]]
[[Category: SO4]]
[[Category: delta-tcr]]
[[Category: glycoprotein]]
[[Category: immune system]]
[[Category: signa immunoglobulin fold]]
[[Category: t-cell]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:06:55 2008''

Latest revision as of 09:49, 30 October 2024

Structure of the MHC Class I Homolog MICBStructure of the MHC Class I Homolog MICB

Structural highlights

1je6 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.5Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MICB_HUMAN Genetic variations in MICA are a cause of susceptibility to rheumatoid arthritis (RA) [MIM:180300. It is a systemic inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Note=The MICB*004 allele is associated with rheumatoid arthritis. Note=Genetic variation in MICB is associated with cytomegalovirus and herpes simplex virus I seropositivity and this may be associated with schizophrenia risk.

Function

MICB_HUMAN Seems to have no role in antigen presentation. Acts as a stress-induced self-antigen that is recognized by gamma delta T cells. Ligand for the KLRK1/NKG2D receptor. Binding to KLRK1 leads to cell lysis.[1] [2]

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

MIC-A and MIC-B are distant MHC class I homologs that serve as stress-inducible Ags on epithelial and epithelially derived cells. They are ligands for the widely expressed activating immunoreceptor NKG2D. To define the structural and functional consequences of sequence differences between MIC-A and MIC-B and between alleles of MIC-A and alleles of MIC-B, we determined the crystal structure of one allele of human MIC-B. Comparisons between the two previously reported MIC-A crystal structures and the MIC-B crystal structure show that, as expected, MIC-B is very similar in structure to MIC-A and likely interacts with NKG2D in an analogous manner. The interdomain flexibility observed in the MIC-A structures, a feature unique to MIC proteins among MHC class I proteins and homologs, is also displayed by MIC-B, with an interdomain relationship intermediate between the two examples of MIC-A structures. Mapping sequence variations onto the structures of MIC-A and MIC-B reveals patterns completely distinct from those displayed by classical MHC class I proteins, with a number of substitutions falling on positions likely to affect interactions with NKG2D, but with other positions lying distant from the NKG2D binding sites or buried within the core of the proteins.

Structural studies of allelic diversity of the MHC class I homolog MIC-B, a stress-inducible ligand for the activating immunoreceptor NKG2D.,Holmes MA, Li P, Petersdorf EW, Strong RK J Immunol. 2002 Aug 1;169(3):1395-400. PMID:12133964[3]

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

References

  1. Groh V, Steinle A, Bauer S, Spies T. Recognition of stress-induced MHC molecules by intestinal epithelial gammadelta T cells. Science. 1998 Mar 13;279(5357):1737-40. PMID:9497295
  2. Steinle A, Li P, Morris DL, Groh V, Lanier LL, Strong RK, Spies T. Interactions of human NKG2D with its ligands MICA, MICB, and homologs of the mouse RAE-1 protein family. Immunogenetics. 2001 May-Jun;53(4):279-87. PMID:11491531
  3. Holmes MA, Li P, Petersdorf EW, Strong RK. Structural studies of allelic diversity of the MHC class I homolog MIC-B, a stress-inducible ligand for the activating immunoreceptor NKG2D. J Immunol. 2002 Aug 1;169(3):1395-400. PMID:12133964

1je6, resolution 2.50Å

Drag the structure with the mouse to rotate

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