4zjg

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of native alpha-2-macroglobulin from Escherichia coli spanning domains MG0-NIE-MG1.

Structural highlights

4zjg is a 1 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A2MG_ECOLI Protects the bacterial cell from host peptidases (PubMed:18697741, PubMed:26100869, PubMed:26143919). Acts by a 'trapping' mechanism. Cleavage of the bait-region domain by host peptidases leads to a global conformational change, which results in entrapment of the host peptidase and activation of the thioester bond that covalently binds the attacking host peptidase (PubMed:26100869, PubMed:26143919). Trapped peptidases are still active except against very large substrates (PubMed:26100869). May protect the entire periplam, including the lipoproteins anchored to the periplasmic side of the outer membrane, against intruding endopeptidases (PubMed:26100869).^[1] ^[2] ^[3]

Publication Abstract from PubMed

The survival of commensal bacteria requires them to evade host peptidases. Gram-negative bacteria from the human gut microbiome encode a relative of the human endopeptidase inhibitor, alpha2-macroglobulin (alpha2M). Escherichia coli alpha2M (ECAM) is a approximately 180-kDa multidomain membrane-anchored pan-peptidase inhibitor, which is cleaved by host endopeptidases in an accessible bait region. Structural studies by electron microscopy and crystallography reveal that this cleavage causes major structural rearrangement of more than half the 13-domain structure from a native to a compact induced form. It also exposes a reactive thioester bond, which covalently traps the peptidase. Subsequently, peptidase-laden ECAM is shed from the membrane and may dimerize. Trapped peptidases are still active except against very large substrates, so inhibition potentially prevents damage of large cell envelope components, but not host digestion. Mechanistically, these results document a novel monomeric "snap trap."

Structural and functional insights into Escherichia coli alpha2-macroglobulin endopeptidase snap-trap inhibition.,Garcia-Ferrer I, Arede P, Gomez-Blanco J, Luque D, Duquerroy S, Caston JR, Goulas T, Gomis-Ruth FX Proc Natl Acad Sci U S A. 2015 Jun 22. pii: 201506538. PMID:26100869^[4]

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

References

↑ Doan N, Gettins PG. alpha-Macroglobulins are present in some gram-negative bacteria: characterization of the alpha2-macroglobulin from Escherichia coli. J Biol Chem. 2008 Oct 17;283(42):28747-56. PMID:18697741 doi:10.1074/jbc.M803127200
↑ Garcia-Ferrer I, Arede P, Gomez-Blanco J, Luque D, Duquerroy S, Caston JR, Goulas T, Gomis-Ruth FX. Structural and functional insights into Escherichia coli alpha2-macroglobulin endopeptidase snap-trap inhibition. Proc Natl Acad Sci U S A. 2015 Jun 22. pii: 201506538. PMID:26100869 doi:http://dx.doi.org/10.1073/pnas.1506538112
↑ Fyfe CD, Grinter R, Josts I, Mosbahi K, Roszak AW, Cogdell RJ, Wall DM, Burchmore RJ, Byron O, Walker D. Structure of protease-cleaved Escherichia coli alpha-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment. Acta Crystallogr D Biol Crystallogr. 2015 Jul 1;71(Pt 7):1478-86. doi:, 10.1107/S1399004715008548. Epub 2015 Jun 30. PMID:26143919 doi:http://dx.doi.org/10.1107/S1399004715008548
↑ Garcia-Ferrer I, Arede P, Gomez-Blanco J, Luque D, Duquerroy S, Caston JR, Goulas T, Gomis-Ruth FX. Structural and functional insights into Escherichia coli alpha2-macroglobulin endopeptidase snap-trap inhibition. Proc Natl Acad Sci U S A. 2015 Jun 22. pii: 201506538. PMID:26100869 doi:http://dx.doi.org/10.1073/pnas.1506538112

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/4zjg"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4zjg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZJG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZJG FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></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]] 2.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=4zjg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zjg OCA], [https://pdbe.org/4zjg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zjg RCSB], [https://www.ebi.ac.uk/pdbsum/4zjg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zjg ProSAT]</span></td></tr>
 </table>
 == Function ==
-[https://www.uniprot.org/uniprot/A2MG_ECOLI A2MG_ECOLI] Protects the bacterial cell from host peptidases (PubMed:18697741, PubMed:26143919, PubMed:26100869). Acts by a 'trapping' mechanism. Cleavage of the bait-region domain by host peptidases leads to a global conformational change, which results in entrapment of the host peptidase and activation of the thioester bond that covalently binds the attacking host peptidase (PubMed:26143919, PubMed:26100869). Trapped peptidases are still active except against very large substrates (PubMed:26100869). May protect the entire periplam, including the lipoproteins anchored to the periplasmic side of the outer membrane, against intruding endopeptidases (PubMed:26100869).<ref>PMID:18697741</ref> <ref>PMID:26100869</ref> <ref>PMID:26143919</ref>
+[https://www.uniprot.org/uniprot/A2MG_ECOLI A2MG_ECOLI] Protects the bacterial cell from host peptidases (PubMed:18697741, PubMed:26100869, PubMed:26143919). Acts by a 'trapping' mechanism. Cleavage of the bait-region domain by host peptidases leads to a global conformational change, which results in entrapment of the host peptidase and activation of the thioester bond that covalently binds the attacking host peptidase (PubMed:26100869, PubMed:26143919). Trapped peptidases are still active except against very large substrates (PubMed:26100869). May protect the entire periplam, including the lipoproteins anchored to the periplasmic side of the outer membrane, against intruding endopeptidases (PubMed:26100869).<ref>PMID:18697741</ref> <ref>PMID:26100869</ref> <ref>PMID:26143919</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4zjg

From Proteopedia

Current revision

Crystal structure of native alpha-2-macroglobulin from Escherichia coli spanning domains MG0-NIE-MG1.

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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