2rcs: Difference between revisions

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[[Image:2rcs.png|left|200px]]


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==IMMUNOGLOBULIN 48G7 GERMLINE FAB-AFFINITY MATURATION OF AN ESTEROLYTIC ANTIBODY==
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<StructureSection load='2rcs' size='340' side='right'caption='[[2rcs]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[2rcs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RCS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RCS FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2rcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rcs OCA], [https://pdbe.org/2rcs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rcs RCSB], [https://www.ebi.ac.uk/pdbsum/2rcs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rcs ProSAT]</span></td></tr>
{{STRUCTURE_2rcs|  PDB=2rcs  |  SCENE=  }}
</table>
== Disease ==
[https://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN] Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:[https://omim.org/entry/254500 254500]. MM is a malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. Note=A chromosomal aberration involving IGHG1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus. Translocation t(11;14)(q13;q32) with CCND1; translocation t(4;14)(p16.3;q32.3) with FGFR3; translocation t(6;14)(p25;q32) with IRF4.
== Function ==
[https://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN]
== 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/rc/2rcs_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=2rcs ConSurf].
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== Publication Abstract from PubMed ==
The crystal structures of a germline antibody Fab fragment and its complex with hapten have been solved at 2.1 A resolution. These structures are compared with the corresponding crystal structures of the affinity-matured antibody, 48G7, which has a 30,000 times higher affinity for hapten as a result of nine replacement somatic mutations. Significant changes in the configuration of the combining site occur upon binding of hapten to the germline antibody, whereas hapten binds to the mature antibody by a lock-and-key fit mechanism. The reorganization of the combining site that was nucleated by hapten binding is further optimized by somatic mutations that occur up to 15 from bound hapten. These results suggest that the binding potential of the primary antibody repertoire may be significantly expanded by the ability of germline antibodies to adopt more than one combining-site configuration, with both antigen binding and somatic mutation stabilizing the configuration with optimal hapten complementarity.


===IMMUNOGLOBULIN 48G7 GERMLINE FAB-AFFINITY MATURATION OF AN ESTEROLYTIC ANTIBODY===
Structural insights into the evolution of an antibody combining site.,Wedemayer GJ, Patten PA, Wang LH, Schultz PG, Stevens RC Science. 1997 Jun 13;276(5319):1665-9. PMID:9180069<ref>PMID:9180069</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2rcs" style="background-color:#fffaf0;"></div>


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==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_9180069}}, adds the Publication Abstract to the page
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
(as it appears on PubMed at http://www.pubmed.gov), where 9180069 is the PubMed ID number.
== References ==
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<references/>
{{ABSTRACT_PUBMED_9180069}}
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</StructureSection>
==About this Structure==
2RCS is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RCS OCA].
 
==Reference==
Structural insights into the evolution of an antibody combining site., Wedemayer GJ, Patten PA, Wang LH, Schultz PG, Stevens RC, Science. 1997 Jun 13;276(5319):1665-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9180069 9180069]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Protein complex]]
[[Category: Patten PA]]
[[Category: Patten, P A.]]
[[Category: Schultz PG]]
[[Category: Schultz, P G.]]
[[Category: Stevens RC]]
[[Category: Stevens, R C.]]
[[Category: Wang LH]]
[[Category: Wang, L H.]]
[[Category: Wedemayer GJ]]
[[Category: Wedemayer, G J.]]
[[Category: Affinity maturation]]
[[Category: Catalytic antibody]]
[[Category: Fab]]
[[Category: Germline antibody]]
 
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