View source for 6qfa


==CryoEM structure of a beta3K279T GABA(A)R homomer in complex with histamine and megabody Mb25==
<StructureSection load='6qfa' size='340' side='right'caption='[[6qfa]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6qfa]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori_G27 Helicobacter pylori G27], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QFA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QFA 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]] 2.49&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=HSM:HISTAMINE'>HSM</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=6qfa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qfa OCA], [https://pdbe.org/6qfa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qfa RCSB], [https://www.ebi.ac.uk/pdbsum/6qfa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qfa ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/GBRB3_HUMAN GBRB3_HUMAN] Autism;Childhood absence epilepsy. Disease susceptibility is associated with variations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/GBRB3_HUMAN GBRB3_HUMAN] GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Nanobodies are popular and versatile tools for structural biology. They have a compact single immunoglobulin domain organization, bind target proteins with high affinities while reducing their conformational heterogeneity and stabilize multi-protein complexes. Here we demonstrate that engineered nanobodies can also help overcome two major obstacles that limit the resolution of single-particle cryo-electron microscopy reconstructions: particle size and preferential orientation at the water-air interfaces. We have developed and characterized constructs, termed megabodies, by grafting nanobodies onto selected protein scaffolds to increase their molecular weight while retaining the full antigen-binding specificity and affinity. We show that the megabody design principles are applicable to different scaffold proteins and recognition domains of compatible geometries and are amenable for efficient selection from yeast display libraries. Moreover, we demonstrate that megabodies can be used to obtain three-dimensional reconstructions for membrane proteins that suffer from severe preferential orientation or are otherwise too small to allow accurate particle alignment.

Megabodies expand the nanobody toolkit for protein structure determination by single-particle cryo-EM.,Uchanski T, Masiulis S, Fischer B, Kalichuk V, Lopez-Sanchez U, Zarkadas E, Weckener M, Sente A, Ward P, Wohlkonig A, Zogg T, Remaut H, Naismith JH, Nury H, Vranken W, Aricescu AR, Pardon E, Steyaert J Nat Methods. 2021 Jan;18(1):60-68. doi: 10.1038/s41592-020-01001-6. Epub 2021 Jan, 6. PMID:33408403<ref>PMID:33408403</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6qfa" style="background-color:#fffaf0;"></div>

==See Also==
*[[Kallikrein 3D structures|Kallikrein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Helicobacter pylori G27]]
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Aricescu AR]]
[[Category: Fischer B]]
[[Category: Kalichuk V]]
[[Category: Masiulis S]]
[[Category: Pardon E]]
[[Category: Remaut H]]
[[Category: Steyaert J]]
[[Category: Uchanski T]]
[[Category: Vranken W]]
[[Category: Wohlkoening A]]
[[Category: Zoegg T]]