View source for 4nwu


==Crystal structure of APE1551, an anti-human NGF Fab with a nine amino acid insertion in CDR H1==
<StructureSection load='4nwu' size='340' side='right'caption='[[4nwu]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4nwu]] is a 2 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=4NWU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NWU 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]] 1.602&#8491;</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=4nwu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nwu OCA], [https://pdbe.org/4nwu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nwu RCSB], [https://www.ebi.ac.uk/pdbsum/4nwu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nwu ProSAT]</span></td></tr>
</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] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
During somatic hypermutation (SHM), deamination of cytidine by activation-induced cytidine deaminase (AID) and subsequent DNA repair generates mutations within immunoglobulin V-regions. Nucleotide insertions and deletions (indels) have recently been shown to be critical for the evolution of antibody binding. Affinity maturation of 53 antibodies using in vitro SHM in a non-B cell context was compared with mutation patterns observed for SHM in vivo. The origin and frequency of indels seen during in vitro maturation was similar to that in vivo. Indels are localized to CDRs, and secondary mutations within insertions further optimize antigen binding. Structure determination of an antibody matured in vitro and comparison with human-derived antibodies containing insertions reveals conserved patterns of antibody maturation. These findings indicate that AID acting on V region sequences is sufficient to initiate authentic formation of indels in vitro and in vivo, and that point mutations, indel formation and clonal selection form a robust, tripartite system for antibody evolution.

Nucleotide insertions and deletions complement point mutations to massively expand the diversity created by somatic hypermutation of antibodies.,Bowers PM, Verdino P, Wang Z, da Silva Correia J, Chhoa M, Macondray G, Do M, Neben TY, Horlick RA, Stanfield RL, Wilson IA, King DJ J Biol Chem. 2014 Oct 15. pii: jbc.M114.607176. PMID:25320089<ref>PMID:25320089</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4nwu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Stanfield RL]]
[[Category: Verdino P]]
[[Category: Wilson IA]]