7x4i - Revision history

OCA at 17:47, 29 November 2023

OCA — Wed, 29 Nov 2023 17:47:46 GMT

←Older revision		Revision as of 17:47, 29 November 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7x4i]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus Severe acute respiratory syndrome coronavirus] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7X4I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7X4I FirstGlance]. <br>		<table><tr><td colspan='2'>[[7x4i]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus Severe acute respiratory syndrome coronavirus] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7X4I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7X4I FirstGlance]. <br>
-	</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=7x4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7x4i OCA], [https://pdbe.org/7x4i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7x4i RCSB], [https://www.ebi.ac.uk/pdbsum/7x4i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7x4i ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 3.38Å</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=7x4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7x4i OCA], [https://pdbe.org/7x4i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7x4i RCSB], [https://www.ebi.ac.uk/pdbsum/7x4i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7x4i ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 07:35, 11 January 2023

OCA — Wed, 11 Jan 2023 07:35:53 GMT

←Older revision		Revision as of 07:35, 11 January 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7x4i is ~~ON HOLD~~	+	==Crystal structure of nanobody aSA3 in complex with dimer SARS-CoV-1 RBD==
		+	<StructureSection load='7x4i' size='340' side='right'caption='[[7x4i]], [[Resolution\|resolution]] 3.38Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7x4i]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus Severe acute respiratory syndrome coronavirus] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7X4I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7X4I FirstGlance]. <br>
		+	</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=7x4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7x4i OCA], [https://pdbe.org/7x4i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7x4i RCSB], [https://www.ebi.ac.uk/pdbsum/7x4i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7x4i ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q19QX0_SARS Q19QX0_SARS] Spike protein S1: attaches the virion to the cell membrane by interacting with host receptor, initiating the infection.[HAMAP-Rule:MF_04099] Spike protein S2': Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099] Spike protein S2: mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.[HAMAP-Rule:MF_04099]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Current SARS-CoV-2 Omicron subvariants impose a heavy burden on global health systems by evading immunity from most developed neutralizing antibodies and vaccines. Here, we identified a nanobody (aSA3) that strongly cross-reacts with the receptor binding domain (RBD) of both SARS-CoV-1 and wild-type (WT) SARS-CoV-2. The dimeric construct of aSA3 (aSA3-Fc) tightly binds and potently neutralizes both SARS-CoV-1 and WT SARS-CoV-2. Based on X-ray crystallography, we engineered a bispecific nanobody dimer (2-3-Fc) by fusing aSA3-Fc to aRBD-2, a previously identified broad-spectrum nanobody targeting an RBD epitope distinct from aSA3. 2-3-Fc exhibits single-digit ng/mL neutralizing potency against all major variants of concerns including BA.5. In hamsters, a single systemic dose of 2-3-Fc at 10 mg/kg conferred substantial efficacy against Omicron infection. More importantly, even at three low doses of 0.5 mg/kg, 2-3-Fc prophylactically administered through the intranasal route drastically reduced viral RNA loads and completely eliminated infectious Omicron particles in the trachea and lungs. Finally, we discovered that 2(Y29G)-3-Fc containing a Y29G substitution in aRBD-2 showed better activity than 2-3-Fc in neutralizing BA.2.75, a recent Omicron subvariant that emerged in India. This study expands the arsenal against SARS-CoV-1, provides potential therapeutic and prophylactic candidates that fully cover major SARS-CoV-2 variants, and may offer a simple preventive approach against Omicron and its subvariants.

-	~~Authors: Ma~~, H., ~~Zeng~~, W.H., ~~Jin~~, T.C.	+	A bispecific nanobody dimer broadly neutralizes SARS-CoV-1 & 2 variants of concern and offers substantial protection against Omicron via low-dose intranasal administration.,Ma H, Zhang X, Zeng W, Zhou J, Chi X, Chen S, Zheng P, Wang M, Wu Y, Zhao D, Gong F, Lin H, Sun H, Yu C, Shi Z, Hu X, Zhang H, Jin T, Chiu S Cell Discov. 2022 Dec 9;8(1):132. doi: 10.1038/s41421-022-00497-w. PMID:36494344<ref>PMID:36494344</ref>

-	~~Description: Crystal structure~~ of ~~nanobody aSA3 in complex with dimer SARS~~-~~CoV~~-~~1 RBD~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Ma, H~~]]	+	<div class="pdbe-citations 7x4i" style="background-color:#fffaf0;"></div>
-	[[Category: Jin~~, T.C~~]]	+	== References ==
-	[[Category: ~~Zeng, W.~~H]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Severe acute respiratory syndrome coronavirus]]
		+	[[Category: Vicugna pacos]]
		+	[[Category: Jin TC]]
		+	[[Category: Ma H]]
		+	[[Category: Zeng WH]]

OCA: Protected "7x4i" [edit=sysop:move=sysop]

OCA — Wed, 09 Mar 2022 05:07:17 GMT

Protected "7x4i" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:07, 9 March 2022

OCA: New page: '''Unreleased structure''' The entry 7x4i is ON HOLD Authors: Ma, H., Zeng, W.H., Jin, T.C. Description: Crystal structure of nanobody aSA3 in complex with dimer SARS-CoV-1 RBD [[Categ...

OCA — Wed, 09 Mar 2022 05:07:16 GMT

New page: '''Unreleased structure''' The entry 7x4i is ON HOLD Authors: Ma, H., Zeng, W.H., Jin, T.C. Description: Crystal structure of nanobody aSA3 in complex with dimer SARS-CoV-1 RBD [[Categ...

New page

'''Unreleased structure'''

The entry 7x4i is ON HOLD

Authors: Ma, H., Zeng, W.H., Jin, T.C.

Description: Crystal structure of nanobody aSA3 in complex with dimer SARS-CoV-1 RBD
[[Category: Unreleased Structures]]
[[Category: Ma, H]]
[[Category: Jin, T.C]]
[[Category: Zeng, W.H]]