View source for 8vgo


==CryoEM structure of CD20 in complex with engineered conformationally rigid Rituximab.4DS Fab==
<StructureSection load='8vgo' size='340' side='right'caption='[[8vgo]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8vgo]] is a 6 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=8VGO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VGO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.6&#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=8vgo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vgo OCA], [https://pdbe.org/8vgo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vgo RCSB], [https://www.ebi.ac.uk/pdbsum/8vgo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vgo ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CD20_HUMAN CD20_HUMAN] Defects in MS4A1 are the cause of immunodeficiency common variable type 5 (CVID5) [MIM:[https://omim.org/entry/613495 613495]; also called antibody deficiency due to CD20 defect. CVID5 is a primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.<ref>PMID:20038800</ref> 
== Function ==
[https://www.uniprot.org/uniprot/CD20_HUMAN CD20_HUMAN] This protein may be involved in the regulation of B-cell activation and proliferation.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
High-resolution structures of proteins are critical to understanding molecular mechanisms of biological processes and in the discovery of therapeutic molecules. Cryo-EM has revolutionized structure determination of large proteins and their complexes(1), but a vast majority of proteins that underlie human diseases are small (&lt; 50 kDa) and usually beyond its reach due to low signal-to-noise images and difficulties in particle alignment(2). Current strategies to overcome this problem increase the overall size of small protein targets using scaffold proteins that bind to the target, but are limited by inherent flexibility and not being bound to their targets in a rigid manner, resulting in the target being poorly resolved compared to the scaffolds(3-11). Here we present an iteratively engineered molecular design for transforming Fabs (antibody fragments), into conformationally rigid scaffolds (Rigid-Fabs) that, when bound to small proteins (~20 kDa), can enable high-resolution structure determination using cryo-EM. This design introduces multiple disulfide bonds at strategic locations, generates a well-folded Fab constrained into a rigid conformation and can be applied to Fabs from various species, isotypes and chimeric Fabs. We present examples of the Rigid Fab design enabling high-resolution (2.3-2.5 A) structures of small proteins, Ang2 (26 kDa) and KRAS (21 kDa) by cryo-EM. The strategies for designing disulfide constrained Rigid Fabs in our work thus establish a general approach to overcome the target size limitation of single particle cryo-EM.

Disulfi de constrained Fabs overcome target size limitation for high-resolution single-particle cryo-EM.,Kung JE, Johnson MC, Jao CC, Arthur CP, Tegunov D, Rohou A, Sudhamsu J bioRxiv [Preprint]. 2024 May 13:2024.05.10.593593. doi: , 10.1101/2024.05.10.593593. PMID:38798381<ref>PMID:38798381</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8vgo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arthur CP]]
[[Category: Jao CC]]
[[Category: Kung JE]]
[[Category: Sudhamsu J]]