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3ffk

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Revision as of 06:40, 1 November 2017

Crystal structure of human Gelsolin domains G1-G3 bound to Actin

Structural highlights

3ffk is a 4 chain structure with sequence from Human and Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1d0n, 1h1v, 1p8x, 1p8z, 1rgi, 2fgh
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] [ACTS_RABIT] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

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

Gelsolin consists of six homologous domains (G1-G6), each containing a conserved Ca-binding site. Occupation of a subset of these sites enables gelsolin to sever and cap actin filaments in a Ca-dependent manner. Here, we present the structures of Ca-free human gelsolin and of Ca-bound human G1-G3 in a complex with actin. These structures closely resemble those determined previously for equine gelsolin. However, the G2 Ca-binding site is occupied in the human G1-G3/actin structure, whereas it is vacant in the equine version. In-depth comparison of the Ca-free and Ca-activated, actin-bound human gelsolin structures suggests G2 and G6 to be cooperative in binding Ca(2+) and responsible for opening the G2-G6 latch to expose the F-actin-binding site on G2. Mutational analysis of the G2 and G6 Ca-binding sites demonstrates their interdependence in maintaining the compact structure in the absence of calcium. Examination of Ca binding by G2 in human G1-G3/actin reveals that the Ca(2+) locks the G2-G3 interface. Thermal denaturation studies of G2-G3 indicate that Ca binding stabilizes this fragment, driving it into the active conformation. The G2 Ca-binding site is mutated in gelsolin from familial amyloidosis (Finnish-type) patients. This disease initially proceeds through protease cleavage of G2, ultimately to produce a fragment that forms amyloid fibrils. The data presented here support a mechanism whereby the loss of Ca binding by G2 prolongs the lifetime of partially activated, intermediate conformations in which the protease cleavage site is exposed.

Ca2+ binding by domain 2 plays a critical role in the activation and stabilization of gelsolin.,Nag S, Ma Q, Wang H, Chumnarnsilpa S, Lee WL, Larsson M, Kannan B, Hernandez-Valladares M, Burtnick LD, Robinson RC Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13713-8. Epub 2009 Aug 4. PMID:19666512^[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
↑ Nag S, Ma Q, Wang H, Chumnarnsilpa S, Lee WL, Larsson M, Kannan B, Hernandez-Valladares M, Burtnick LD, Robinson RC. Ca2+ binding by domain 2 plays a critical role in the activation and stabilization of gelsolin. Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13713-8. Epub 2009 Aug 4. PMID:19666512

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ffk"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human Gelsolin domains G1-G3 bound to Actin==
 <StructureSection load='3ffk' size='340' side='right' caption='[[3ffk]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1d0n|1d0n]], [[1h1v|1h1v]], [[1p8x|1p8x]], [[1p8z|1p8z]], [[1rgi|1rgi]], [[2fgh|2fgh]]</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=3ffk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ffk OCA], [http://pdbe.org/3ffk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ffk RCSB], [http://www.ebi.ac.uk/pdbsum/3ffk PDBsum]</span></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=3ffk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ffk OCA], [http://pdbe.org/3ffk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ffk RCSB], [http://www.ebi.ac.uk/pdbsum/3ffk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ffk ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 31: / Line 32: @@
 </div>
 <div class="pdbe-citations 3ffk" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Actin|Actin]]
-*[[Gelsolin|Gelsolin]]
 == References ==
 <references/>

3ffk

From Proteopedia

Revision as of 06:40, 1 November 2017

Crystal structure of human Gelsolin domains G1-G3 bound to Actin

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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