View source for 8ecz


==Bovine Fab 4C1==
<StructureSection load='8ecz' size='340' side='right'caption='[[8ecz]], [[Resolution|resolution]] 2.82&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ecz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ECZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ECZ 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]] 2.82&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=8ecz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ecz OCA], [https://pdbe.org/8ecz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ecz RCSB], [https://www.ebi.ac.uk/pdbsum/8ecz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ecz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/IGLC2_HUMAN IGLC2_HUMAN] Constant region of immunoglobulin light chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:20176268, PubMed:22158414). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:17576170, PubMed:20176268).<ref>PMID:17576170</ref> <ref>PMID:20176268</ref> <ref>PMID:22158414</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cows produce antibodies with a disulfide-bonded antigen-binding domain embedded within ultralong heavy chain third complementarity determining regions. This "knob" domain is analogous to natural cysteine-rich peptides such as knottins in that it is small and stable but can accommodate diverse loops and disulfide bonding patterns. We immunized cattle with SARS-CoV-2 spike and found ultralong CDR H3 antibodies that could neutralize several viral variants at picomolar IC(50) potencies in vitro and could protect from disease in vivo. The independent CDR H3 peptide knobs were expressed and maintained the properties of the parent antibodies. The knob interaction with SARS-CoV-2 spike was revealed by electron microscopy, X-ray crystallography, NMR spectroscopy, and mass spectrometry and established ultralong CDR H3-derived knobs as the smallest known recombinant independent antigen-binding fragment. Unlike other vertebrate antibody fragments, these knobs are not reliant on the immunoglobulin domain and have potential as a new class of therapeutics.

The smallest functional antibody fragment: Ultralong CDR H3 antibody knob regions potently neutralize SARS-CoV-2.,Huang R, Warner Jenkins G, Kim Y, Stanfield RL, Singh A, Martinez-Yamout M, Kroon GJ, Torres JL, Jackson AM, Kelley A, Shaabani N, Zeng B, Bacica M, Chen W, Warner C, Radoicic J, Joh J, Dinali Perera K, Sang H, Kim T, Yao J, Zhao F, Sok D, Burton DR, Allen J, Harriman W, Mwangi W, Chung D, Teijaro JR, Ward AB, Dyson HJ, Wright PE, Wilson IA, Chang KO, McGregor D, Smider VV Proc Natl Acad Sci U S A. 2023 Sep 26;120(39):e2303455120. doi: , 10.1073/pnas.2303455120. Epub 2023 Sep 18. PMID:37722054<ref>PMID:37722054</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ecz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Stanfield RL]]
[[Category: Wilson IA]]