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6q9z

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Revision as of 09:04, 5 February 2020

Crystal structure of the pathological G167R variant of calcium-free human gelsolin,

Structural highlights

6q9z is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3ffn, 6q9r
Gene:	GSN (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[GELS_HUMAN] Defects in GSN are the cause of amyloidosis type 5 (AMYL5) [MIM:105120]; also known as familial amyloidosis Finnish type. AMYL5 is a hereditary generalized amyloidosis due to gelsolin amyloid deposition. It is typically characterized by cranial neuropathy and lattice corneal dystrophy. Most patients have modest involvement of internal organs, but severe systemic disease can develop in some individuals causing peripheral polyneuropathy, amyloid cardiomyopathy, and nephrotic syndrome leading to renal failure.^[1] ^[2] ^[3] ^[4]

Function

[GELS_HUMAN] Calcium-regulated, actin-modulating protein that binds to the plus (or barbed) ends of actin monomers or filaments, preventing monomer exchange (end-blocking or capping). It can promote the assembly of monomers into filaments (nucleation) as well as sever filaments already formed. Plays a role in ciliogenesis.^[5]

Publication Abstract from PubMed

Mutations in the gelsolin protein are responsible for a rare conformational disease known as AGel amyloidosis. Four of these mutations are hosted by the second domain of the protein (G2): D187N/Y, G167R and N184K. The impact of the latter has been so far evaluated only by studies on the isolated G2. Here we report the characterization of full-length gelsolin carrying the N184K mutation and compare the findings with those obtained on the wild type and the other variants. The crystallographic structure of the N184K variant in the Ca(2+)-free conformation shows remarkable similarities with the wild type protein. Only minimal local rearrangements can be observed and the mutant is as efficient as the wild type in severing filamentous actin. However, the thermal stability of the pathological variant is compromised in the Ca(2+)-free conditions. These data suggest that the N to K substitution causes a local disruption of the H-bond network in the core of the G2 domain. Such a subtle rearrangement of the connections does not lead to significant conformational changes but severely affects the stability of the protein.

The structure of N184K amyloidogenic variant of gelsolin highlights the role of the H-bond network for protein stability and aggregation properties.,de Rosa M, Barbiroli A, Boni F, Scalone E, Mattioni D, Vanoni MA, Patrone M, Bollati M, Mastrangelo E, Giorgino T, Milani M Eur Biophys J. 2019 Nov 13. pii: 10.1007/s00249-019-01409-9. doi:, 10.1007/s00249-019-01409-9. PMID:31724080^[6]

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

References

↑ Haltia M, Prelli F, Ghiso J, Kiuru S, Somer H, Palo J, Frangione B. Amyloid protein in familial amyloidosis (Finnish type) is homologous to gelsolin, an actin-binding protein. Biochem Biophys Res Commun. 1990 Mar 30;167(3):927-32. PMID:2157434
↑ Maury CP, Alli K, Baumann M. Finnish hereditary amyloidosis. Amino acid sequence homology between the amyloid fibril protein and human plasma gelsoline. FEBS Lett. 1990 Jan 15;260(1):85-7. PMID:2153578
↑ Ghiso J, Haltia M, Prelli F, Novello J, Frangione B. Gelsolin variant (Asn-187) in familial amyloidosis, Finnish type. Biochem J. 1990 Dec 15;272(3):827-30. PMID:2176481
↑ de la Chapelle A, Tolvanen R, Boysen G, Santavy J, Bleeker-Wagemakers L, Maury CP, Kere J. Gelsolin-derived familial amyloidosis caused by asparagine or tyrosine substitution for aspartic acid at residue 187. Nat Genet. 1992 Oct;2(2):157-60. PMID:1338910 doi:http://dx.doi.org/10.1038/ng1092-157
↑ Kim J, Lee JE, Heynen-Genel S, Suyama E, Ono K, Lee K, Ideker T, Aza-Blanc P, Gleeson JG. Functional genomic screen for modulators of ciliogenesis and cilium length. Nature. 2010 Apr 15;464(7291):1048-51. doi: 10.1038/nature08895. PMID:20393563 doi:10.1038/nature08895
↑ de Rosa M, Barbiroli A, Boni F, Scalone E, Mattioni D, Vanoni MA, Patrone M, Bollati M, Mastrangelo E, Giorgino T, Milani M. The structure of N184K amyloidogenic variant of gelsolin highlights the role of the H-bond network for protein stability and aggregation properties. Eur Biophys J. 2019 Nov 13. pii: 10.1007/s00249-019-01409-9. doi:, 10.1007/s00249-019-01409-9. PMID:31724080 doi:http://dx.doi.org/10.1007/s00249-019-01409-9

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6q9z"

@@ Line 3: / Line 3: @@
 <StructureSection load='6q9z' size='340' side='right'caption='[[6q9z]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6q9z]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q9Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6Q9Z FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6q9z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q9Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6Q9Z FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ffn|3ffn]], [[6q9r|6q9r]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GSN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6q9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q9z OCA], [http://pdbe.org/6q9z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q9z RCSB], [http://www.ebi.ac.uk/pdbsum/6q9z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q9z ProSAT]</span></td></tr>
 </table>
@@ Line 25: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Boni, F]]

6q9z

From Proteopedia

Revision as of 09:04, 5 February 2020

Crystal structure of the pathological G167R variant of calcium-free human gelsolin,

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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