8gni

From Proteopedia

(Difference between revisions)

Revision as of 07:34, 18 January 2023

Human SARM1 bounded with NMN and Nanobody-C6, Conformation 1

Structural highlights

8gni is a 3 chain structure with sequence from Homo sapiens and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SARM1_HUMAN Negative regulator of MYD88- and TRIF-dependent toll-like receptor signaling pathway which plays a pivotal role in activating axonal degeneration following injury. Promotes Wallerian degeneration an injury-induced axonal death pathway which involves degeneration of an axon distal to the injury site. Can activate neuronal death in response to stress. Regulates dendritic arborization through the MAPK4-JNK pathway. Involved in innate immune response. Inhibits both TICAM1/TRIF- and MYD88-dependent activation of JUN/AP-1, TRIF-dependent activation of NF-kappa-B and IRF3, and the phosphorylation of MAPK14/p38.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Sterile alpha (SAM) and Toll/interleukin-1 receptor (TIR) motif containing 1 (SARM1) is an autoinhibitory NAD-consuming enzyme that is activated by the accumulation of nicotinamide mononucleotide (NMN) during axonal injury. Its activation mechanism is not fully understood. Here, we generate a nanobody, Nb-C6, that specifically recognizes NMN-activated SARM1. Nb-C6 stains only the activated SARM1 in cells stimulated with CZ-48, a permeant mimetic of NMN, and partially activates SARM1 in vitro and in cells. Cryo-EM of NMN/SARM1/Nb-C6 complex shows an octameric structure with ARM domains bending significantly inward and swinging out together with TIR domains. Nb-C6 binds to SAM domain of the activated SARM1 and stabilized its ARM domain. Mass spectrometry analyses indicate that the activated SARM1 in solution is highly dynamic and that the neighboring TIRs form transient dimers via the surface close to one BB loop. We show that Nb-C6 is a valuable tool for studies of SARM1 activation.

A conformation-specific nanobody targeting the nicotinamide mononucleotide-activated state of SARM1.,Hou YN, Cai Y, Li WH, He WM, Zhao ZY, Zhu WJ, Wang Q, Mai X, Liu J, Lee HC, Stjepanovic G, Zhang H, Zhao YJ Nat Commun. 2022 Dec 22;13(1):7898. doi: 10.1038/s41467-022-35581-y. PMID:36550129^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Liberati NT, Fitzgerald KA, Kim DH, Feinbaum R, Golenbock DT, Ausubel FM. Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response. Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6593-8. PMID:15123841 doi:http://dx.doi.org/10.1073/pnas.0308625101
↑ Carty M, Goodbody R, Schroder M, Stack J, Moynagh PN, Bowie AG. The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling. Nat Immunol. 2006 Oct;7(10):1074-81. doi: 10.1038/ni1382. Epub 2006 Sep 10. PMID:16964262 doi:http://dx.doi.org/10.1038/ni1382
↑ O'Neill LA. DisSARMing Toll-like receptor signaling. Nat Immunol. 2006 Oct;7(10):1023-5. doi: 10.1038/ni1006-1023. PMID:16985498 doi:http://dx.doi.org/10.1038/ni1006-1023
↑ Peng J, Yuan Q, Lin B, Panneerselvam P, Wang X, Luan XL, Lim SK, Leung BP, Ho B, Ding JL. SARM inhibits both TRIF- and MyD88-mediated AP-1 activation. Eur J Immunol. 2010 Jun;40(6):1738-47. doi: 10.1002/eji.200940034. PMID:20306472 doi:http://dx.doi.org/10.1002/eji.200940034
↑ Hou YN, Cai Y, Li WH, He WM, Zhao ZY, Zhu WJ, Wang Q, Mai X, Liu J, Lee HC, Stjepanovic G, Zhang H, Zhao YJ. A conformation-specific nanobody targeting the nicotinamide mononucleotide-activated state of SARM1. Nat Commun. 2022 Dec 22;13(1):7898. doi: 10.1038/s41467-022-35581-y. PMID:36550129 doi:http://dx.doi.org/10.1038/s41467-022-35581-y

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8gni"

Categories: Homo sapiens | Large Structures | Vicugna pacos | Cai Y | Zhang H

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8gni is ON HOLD
+==Human SARM1 bounded with NMN and Nanobody-C6, Conformation 1==
+<StructureSection load='8gni' size='340' side='right'caption='[[8gni]], [[Resolution|resolution]] 3.74&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8gni]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=8GNI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GNI FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NMN:BETA-NICOTINAMIDE+RIBOSE+MONOPHOSPHATE'>NMN</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=8gni FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gni OCA], [https://pdbe.org/8gni PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gni RCSB], [https://www.ebi.ac.uk/pdbsum/8gni PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gni ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/SARM1_HUMAN SARM1_HUMAN] Negative regulator of MYD88- and TRIF-dependent toll-like receptor signaling pathway which plays a pivotal role in activating axonal degeneration following injury. Promotes Wallerian degeneration an injury-induced axonal death pathway which involves degeneration of an axon distal to the injury site. Can activate neuronal death in response to stress. Regulates dendritic arborization through the MAPK4-JNK pathway. Involved in innate immune response. Inhibits both TICAM1/TRIF- and MYD88-dependent activation of JUN/AP-1, TRIF-dependent activation of NF-kappa-B and IRF3, and the phosphorylation of MAPK14/p38.<ref>PMID:15123841</ref> <ref>PMID:16964262</ref> <ref>PMID:16985498</ref> <ref>PMID:20306472</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Sterile alpha (SAM) and Toll/interleukin-1 receptor (TIR) motif containing 1 (SARM1) is an autoinhibitory NAD-consuming enzyme that is activated by the accumulation of nicotinamide mononucleotide (NMN) during axonal injury. Its activation mechanism is not fully understood. Here, we generate a nanobody, Nb-C6, that specifically recognizes NMN-activated SARM1. Nb-C6 stains only the activated SARM1 in cells stimulated with CZ-48, a permeant mimetic of NMN, and partially activates SARM1 in vitro and in cells. Cryo-EM of NMN/SARM1/Nb-C6 complex shows an octameric structure with ARM domains bending significantly inward and swinging out together with TIR domains. Nb-C6 binds to SAM domain of the activated SARM1 and stabilized its ARM domain. Mass spectrometry analyses indicate that the activated SARM1 in solution is highly dynamic and that the neighboring TIRs form transient dimers via the surface close to one BB loop. We show that Nb-C6 is a valuable tool for studies of SARM1 activation.
-Authors: Cai, Y., Zhang, H.
+A conformation-specific nanobody targeting the nicotinamide mononucleotide-activated state of SARM1.,Hou YN, Cai Y, Li WH, He WM, Zhao ZY, Zhu WJ, Wang Q, Mai X, Liu J, Lee HC, Stjepanovic G, Zhang H, Zhao YJ Nat Commun. 2022 Dec 22;13(1):7898. doi: 10.1038/s41467-022-35581-y. PMID:36550129<ref>PMID:36550129</ref>
-Description: Human SARM1 bounded with NMN and Nanobody-C6, Conformation 1
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Zhang, H]]
+<div class="pdbe-citations 8gni" style="background-color:#fffaf0;"></div>
-[[Category: Cai, Y]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Vicugna pacos]]
+[[Category: Cai Y]]
+[[Category: Zhang H]]

8gni

From Proteopedia

Revision as of 07:34, 18 January 2023

Human SARM1 bounded with NMN and Nanobody-C6, Conformation 1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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