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1gqm

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Revision as of 11:34, 10 May 2019

The structure of S100A12 in a hexameric form and its proposed role in receptor signalling

Structural highlights

1gqm is a 12 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1e8a
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[S10AC_HUMAN] S100A12 is a calcium-, zinc- and copper-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. Its proinflammatory activity involves recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to receptor for advanced glycation endproducts (AGER). Binding to AGER activates the MAP-kinase and NF-kappa-B signaling pathways leading to production of proinflammatory cytokines and up-regulation of cell adhesion molecules ICAM1 and VCAM1. Acts as a monocyte and mast cell chemoattractant. Can stimulate mast cell degranulation and activation which generates chemokines, histamine and cytokines inducing further leukocyte recruitment to the sites of inflammation. Can inhibit the activity of matrix metalloproteinases; MMP2, MMP3 and MMP9 by chelating Zn(2+) from their active sites. Possesses filariacidal and filariastatic activity. Calcitermin possesses antifungal activity against C.albicans and is also active against E.coli and P.aeruginosa but not L.monocytogenes and S.aureus.^[1] ^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

S100A12 is a member of the S100 subfamily of EF-hand calcium-binding proteins; it has been shown to be one of the ligands of the 'receptor for advanced glycation end products' (RAGE) that belongs to the immunoglobulin superfamily and is involved in diabetes, Alzheimer's disease, inflammation and tumour invasion. The structure of the dimeric form of native S100A12 from human granulocytes in the presence of calcium in space group R3 has previously been reported. Here, the structure of a second crystal form in space group P2(1) (unit-cell parameters a = 53.9, b = 100.5, c = 112.7A, beta = 94.6 degrees) solved at 2.7A resolution by molecular replacement using the R3 structure as a search model is reported. Like most S100 proteins, S100A12 is a dimer. However, in the P2(1) crystal form dimers of S100A12 are arranged in a spherical hexameric assembly with an external diameter of about 55 A stabilized by calcium ions bound between adjacent dimers. The putative target-binding sites of S100A12 are located at the outer surface of the hexamer, making it possible for the hexamer to bind several targets. It is proposed that the S100A12 hexameric assembly might interact with three extracellular domains of the receptor, bringing them together into large trimeric assemblies.

The structure of S100A12 in a hexameric form and its proposed role in receptor signalling.,Moroz OV, Antson AA, Dodson EJ, Burrell HJ, Grist SJ, Lloyd RM, Maitland NJ, Dodson GG, Wilson KS, Lukanidin E, Bronstein IB Acta Crystallogr D Biol Crystallogr. 2002 Mar;58(Pt 3):407-13. Epub 2002, Feb 21. PMID:11856825^[5]

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

References

↑ Cole AM, Kim YH, Tahk S, Hong T, Weis P, Waring AJ, Ganz T. Calcitermin, a novel antimicrobial peptide isolated from human airway secretions. FEBS Lett. 2001 Aug 24;504(1-2):5-10. PMID:11522286
↑ Yang Z, Yan WX, Cai H, Tedla N, Armishaw C, Di Girolamo N, Wang HW, Hampartzoumian T, Simpson JL, Gibson PG, Hunt J, Hart P, Hughes JM, Perry MA, Alewood PF, Geczy CL. S100A12 provokes mast cell activation: a potential amplification pathway in asthma and innate immunity. J Allergy Clin Immunol. 2007 Jan;119(1):106-14. Epub 2006 Oct 6. PMID:17208591 doi:http://dx.doi.org/10.1016/j.jaci.2006.08.021
↑ Yan WX, Armishaw C, Goyette J, Yang Z, Cai H, Alewood P, Geczy CL. Mast cell and monocyte recruitment by S100A12 and its hinge domain. J Biol Chem. 2008 May 9;283(19):13035-43. doi: 10.1074/jbc.M710388200. Epub 2008 , Feb 21. PMID:18292089 doi:http://dx.doi.org/10.1074/jbc.M710388200
↑ Moroz OV, Burkitt W, Wittkowski H, He W, Ianoul A, Novitskaya V, Xie J, Polyakova O, Lednev IK, Shekhtman A, Derrick PJ, Bjoerk P, Foell D, Bronstein IB. Both Ca2+ and Zn2+ are essential for S100A12 protein oligomerization and function. BMC Biochem. 2009 Apr 23;10:11. doi: 10.1186/1471-2091-10-11. PMID:19386136 doi:http://dx.doi.org/10.1186/1471-2091-10-11
↑ Moroz OV, Antson AA, Dodson EJ, Burrell HJ, Grist SJ, Lloyd RM, Maitland NJ, Dodson GG, Wilson KS, Lukanidin E, Bronstein IB. The structure of S100A12 in a hexameric form and its proposed role in receptor signalling. Acta Crystallogr D Biol Crystallogr. 2002 Mar;58(Pt 3):407-13. Epub 2002, Feb 21. PMID:11856825

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1gqm"

@@ Line 1: / Line 1: @@
 ==The structure of S100A12 in a hexameric form and its proposed role in receptor signalling==
-<StructureSection load='1gqm' size='340' side='right' caption='[[1gqm]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+<StructureSection load='1gqm' size='340' side='right'caption='[[1gqm]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1gqm]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GQM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1GQM FirstGlance]. <br>
@@ Line 29: / Line 29: @@
 </div>
 <div class="pdbe-citations 1gqm" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[S100 protein|S100 protein]]
 == References ==
 <references/>
@@ Line 34: / Line 37: @@
 </StructureSection>
 [[Category: Homo sapiens]]
+[[Category: Large Structures]]
 [[Category: Antson, A A]]
 [[Category: Bronstein, I B]]

1gqm

From Proteopedia

Revision as of 11:34, 10 May 2019

The structure of S100A12 in a hexameric form and its proposed role in receptor signalling

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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