5zz0

From Proteopedia

(Difference between revisions)

Revision as of 11:12, 1 February 2023

HUMAN GELSOLIN FROM RESIDUES GLU28 TO ARG161 WITH CALCIUM

Structural highlights

5zz0 is a 2 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 5dd2. 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

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

Here, we report that minimal functional gelsolin i.e. fragment 28-161 can display F-actin depolymerizing property even after heating the protein to 80 degrees C. Small angle X-ray scattering (SAXS) data analysis confirmed that under Ca(2+)-free conditions, 28-161 associates into monomer to dimer and tetramer, which later forms beta-amyloids, but in presence of Ca(2+), it forms dimers which proceed to non-characterizable aggregates. The dimeric association also explained the observed decrease in ellipticity in circular dichroism experiments with increase in temperature. Importantly, SAXS data based models correlated well with our crystal structure of dimeric state of 28-161. Characterization of higher order association by electron microscopy, Congo red and ThioflavinT staining assays further confirmed that only in absence of Ca(2+) ions, heating transforms 28-161 into beta-amyloids. Gel filtration and other experiments showed that beta-amyloids keep leaching out the monomer, and the release rates could be enhanced by addition of L-Arg to the amyloids. F-actin depolymerization showed that addition of Ca(2+) ions to released monomer initiated the depolymerization activity. Overall, we propose a way to compose a supramolecular assembly which releases functional protein in sustained manner which can be applied for varied potentially therapeutic interventions.

Bonsai Gelsolin Survives Heat Induced Denaturation by Forming beta-Amyloids which Leach Out Functional Monomer.,Badmalia MD, Sharma P, Yadav SPS, Singh S, Khatri N, Garg R, Ashish Sci Rep. 2018 Aug 22;8(1):12602. doi: 10.1038/s41598-018-30951-3. PMID:30135452^[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
↑ Badmalia MD, Sharma P, Yadav SPS, Singh S, Khatri N, Garg R, Ashish. Bonsai Gelsolin Survives Heat Induced Denaturation by Forming beta-Amyloids which Leach Out Functional Monomer. Sci Rep. 2018 Aug 22;8(1):12602. doi: 10.1038/s41598-018-30951-3. PMID:30135452 doi:http://dx.doi.org/10.1038/s41598-018-30951-3

1 Structural highlights
2 Disease
3 Function
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/5zz0"

@@ Line 3: / Line 3: @@
 <StructureSection load='5zz0' size='340' side='right'caption='[[5zz0]], [[Resolution|resolution]] 2.63&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5zz0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZZ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZZ0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5zz0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5dd2 5dd2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZZ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZZ0 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GSN ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=5zz0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zz0 OCA], [https://pdbe.org/5zz0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zz0 RCSB], [https://www.ebi.ac.uk/pdbsum/5zz0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zz0 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/GELS_HUMAN GELS_HUMAN]] Defects in GSN are the cause of amyloidosis type 5 (AMYL5) [MIM:[https://omim.org/entry/105120 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.<ref>PMID:2157434</ref> <ref>PMID:2153578</ref> <ref>PMID:2176481</ref> <ref>PMID:1338910</ref>
+[https://www.uniprot.org/uniprot/GELS_HUMAN GELS_HUMAN] Defects in GSN are the cause of amyloidosis type 5 (AMYL5) [MIM:[https://omim.org/entry/105120 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.<ref>PMID:2157434</ref> <ref>PMID:2153578</ref> <ref>PMID:2176481</ref> <ref>PMID:1338910</ref>
 == Function ==
-[[https://www.uniprot.org/uniprot/GELS_HUMAN 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.<ref>PMID:20393563</ref>
+[https://www.uniprot.org/uniprot/GELS_HUMAN 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.<ref>PMID:20393563</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 28: / Line 27: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Badmalia, M]]
+[[Category: Badmalia M]]
-[[Category: Sharma, P]]
+[[Category: Sharma P]]
-[[Category: Singh, S]]
+[[Category: Singh S]]
-[[Category: Yadav, S P.S]]
+[[Category: Yadav SPS]]
-[[Category: Actin binding protein]]
-[[Category: Metal binding protein]]

5zz0

From Proteopedia

Revision as of 11:12, 1 February 2023

HUMAN GELSOLIN FROM RESIDUES GLU28 TO ARG161 WITH CALCIUM

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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