View source for 8sk7


==Cryo-EM structure of designed Influenza HA binder, HA_20, bound to Influenza HA (Strain: Iowa43)==
<StructureSection load='8sk7' size='340' side='right'caption='[[8sk7]], [[Resolution|resolution]] 2.93&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8sk7]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus Influenza A virus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SK7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SK7 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]] 2.93&#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=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=8sk7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8sk7 OCA], [https://pdbe.org/8sk7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8sk7 RCSB], [https://www.ebi.ac.uk/pdbsum/8sk7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8sk7 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HEMA_I43A0 HEMA_I43A0] Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization either through clathrin-dependent endocytosis or through clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore.[HAMAP-Rule:MF_04072]
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== Publication Abstract from PubMed ==
There has been considerable recent progress in designing new proteins using deep-learning methods(1-9). Despite this progress, a general deep-learning framework for protein design that enables solution of a wide range of design challenges, including de novo binder design and design of higher-order symmetric architectures, has yet to be described. Diffusion models(10,11) have had considerable success in image and language generative modelling but limited success when applied to protein modelling, probably due to the complexity of protein backbone geometry and sequence-structure relationships. Here we show that by fine-tuning the RoseTTAFold structure prediction network on protein structure denoising tasks, we obtain a generative model of protein backbones that achieves outstanding performance on unconditional and topology-constrained protein monomer design, protein binder design, symmetric oligomer design, enzyme active site scaffolding and symmetric motif scaffolding for therapeutic and metal-binding protein design. We demonstrate the power and generality of the method, called RoseTTAFold diffusion (RFdiffusion), by experimentally characterizing the structures and functions of hundreds of designed symmetric assemblies, metal-binding proteins and protein binders. The accuracy of RFdiffusion is confirmed by the cryogenic electron microscopy structure of a designed binder in complex with influenza haemagglutinin that is nearly identical to the design model. In a manner analogous to networks that produce images from user-specified inputs, RFdiffusion enables the design of diverse functional proteins from simple molecular specifications.

De novo design of protein structure and function with RFdiffusion.,Watson JL, Juergens D, Bennett NR, Trippe BL, Yim J, Eisenach HE, Ahern W, Borst AJ, Ragotte RJ, Milles LF, Wicky BIM, Hanikel N, Pellock SJ, Courbet A, Sheffler W, Wang J, Venkatesh P, Sappington I, Torres SV, Lauko A, De Bortoli V, Mathieu E, Ovchinnikov S, Barzilay R, Jaakkola TS, DiMaio F, Baek M, Baker D Nature. 2023 Aug;620(7976):1089-1100. doi: 10.1038/s41586-023-06415-8. Epub 2023 , Jul 11. PMID:37433327<ref>PMID:37433327</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Influenza A virus]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Bennett NR]]
[[Category: Borst AJ]]