9awe: Difference between revisions
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The | ==The crystal structure of an engineered Protein GF with Human Kappa Fab== | ||
<StructureSection load='9awe' size='340' side='right'caption='[[9awe]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9awe]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Streptococcus_sp._'group_G' Streptococcus sp. 'group G']. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9AWE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9AWE 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]] 2.8Å</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=9awe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9awe OCA], [https://pdbe.org/9awe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9awe RCSB], [https://www.ebi.ac.uk/pdbsum/9awe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9awe ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ASF1_YEAST ASF1_YEAST] Histone chaperone that facilitates histone deposition and histone exchange and removal during nucleosome assembly and disassembly. Facilitates histone deposition through both replication-dependent and replication-independent chromatin assembly pathways. Cooperates with chromatin assembly factor 1 (CAF-1) to promote replication-dependent chromatin assembly and with the HIR complex to promote replication-independent chromatin assembly, which may occur during transcription and DNA repair. May be required for the maintenance of a subset of replication elongation factors, including DNA polymerase epsilon, the RFC complex and PCNA, at stalled replication forks. Also required for acetylation of histone H3 on 'Lys-9' and 'Lys-56'.<ref>PMID:9290207</ref> <ref>PMID:10591219</ref> <ref>PMID:11412995</ref> <ref>PMID:11331602</ref> <ref>PMID:11731479</ref> <ref>PMID:11731480</ref> <ref>PMID:11404324</ref> <ref>PMID:11172707</ref> <ref>PMID:11856374</ref> <ref>PMID:11756556</ref> <ref>PMID:12093919</ref> <ref>PMID:14585955</ref> <ref>PMID:15071494</ref> <ref>PMID:15452122</ref> <ref>PMID:15175160</ref> <ref>PMID:15542829</ref> <ref>PMID:15542840</ref> <ref>PMID:15766286</ref> <ref>PMID:16303565</ref> <ref>PMID:15821127</ref> <ref>PMID:15901673</ref> <ref>PMID:16020781</ref> <ref>PMID:16143623</ref> <ref>PMID:16039596</ref> <ref>PMID:15632066</ref> <ref>PMID:15891116</ref> <ref>PMID:16141196</ref> <ref>PMID:15840725</ref> <ref>PMID:16815704</ref> <ref>PMID:16936140</ref> <ref>PMID:16582440</ref> <ref>PMID:16407267</ref> <ref>PMID:17046836</ref> <ref>PMID:16678113</ref> <ref>PMID:16501045</ref> <ref>PMID:16627621</ref> <ref>PMID:17107956</ref> <ref>PMID:17320445</ref> <ref>PMID:14680630</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We have developed a portfolio of antibody-based modules that can be prefabricated as standalone units and snapped together in plug-and-play fashion to create uniquely powerful multifunctional assemblies. The basic building blocks are derived from multiple pairs of native and modified Fab scaffolds and protein G (PG) variants engineered by phage display to introduce high pair-wise specificity. The variety of possible Fab-PG pairings provides a highly orthogonal system that can be exploited to perform challenging cell biology operations in a straightforward manner. The simplest manifestation allows multiplexed antigen detection using PG variants fused to fluorescently labeled SNAP-tags. Moreover, Fabs can be readily attached to a PG-Fc dimer module which acts as the core unit to produce plug-and-play IgG-like assemblies, and the utility can be further expanded to produce bispecific analogs using the "knobs into holes" strategy. These core PG-Fc dimer modules can be made and stored in bulk to produce off-the-shelf customized IgG entities in minutes, not days or weeks by just adding a Fab with the desired antigen specificity. In another application, the bispecific modalities form the building block for fabricating potent bispecific T-cell engagers (BiTEs), demonstrating their efficacy in cancer cell-killing assays. Additionally, the system can be adapted to include commercial antibodies as building blocks, greatly increasing the target space. Crystal structure analysis reveals that a few strategically positioned interactions engender the specificity between the Fab-PG variant pairs, requiring minimal changes to match the scaffolds for different possible combinations. This plug-and-play platform offers a user-friendly and versatile approach to enhance the functionality of antibody-based reagents in cell biology research. | |||
Engineered protein G variants for multifunctional antibody-based assemblies.,Slezak T, O'Leary KM, Li J, Rohaim A, Davydova EK, Kossiakoff AA Protein Sci. 2025 Feb;34(2):e70019. doi: 10.1002/pro.70019. PMID:39865354<ref>PMID:39865354</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Kossiakoff | <div class="pdbe-citations 9awe" style="background-color:#fffaf0;"></div> | ||
[[Category: Slezak | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Streptococcus sp. 'group G']] | |||
[[Category: Kossiakoff AA]] | |||
[[Category: Slezak T]] | |||