1kcq: Difference between revisions
New page: left|200px<br /> <applet load="1kcq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kcq, resolution 1.65Å" /> '''Human Gelsolin Doma... |
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caption="1kcq, resolution 1.65Å" /> | caption="1kcq, resolution 1.65Å" /> | ||
'''Human Gelsolin Domain 2 with a Cd2+ bound'''<br /> | '''Human Gelsolin Domain 2 with a Cd2+ bound'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1KCQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CD as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1KCQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CD:'>CD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KCQ OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: metal binding]] | [[Category: metal binding]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:12:29 2008'' | ||
Revision as of 14:12, 15 February 2008
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Human Gelsolin Domain 2 with a Cd2+ bound
Overview
Mutations in domain 2 (D2, residues 151-266) of the actin-binding protein, gelsolin cause familial amyloidosis-Finnish type (FAF). These mutations, D187N or D187Y, lead to abnormal proteolysis of plasma gelsolin at, residues 172-173 and a second hydrolysis at residue 243, resulting in an, amyloidogenic fragment. Here we present the structure of human gelsolin D2, at 1.65 A and find that Asp 187 is part of a Cd2+ metal-binding site. Two, Ca2+ ions are required for a conformational transition of gelsolin to its, active form. Differential scanning calorimetry (DSC) and molecular, dynamics (MD) simulations suggest that the Cd2+-binding site in D2 is one, of these two Ca2+-binding sites and is essential to the stability of D2., Mutation of Asp 187 to Asn disrupts Ca2+ binding in D2, leading to, instabilities upon Ca2+ activation. These instabilities make the domain a, target for aberrant proteolysis, thereby enacting the first step in the, cascade leading to FAF.
Disease
Known disease associated with this structure: Amyloidosis, Finnish type OMIM:[137350]
About this Structure
1KCQ is a Single protein structure of sequence from Homo sapiens with CD as ligand. Full crystallographic information is available from OCA.
Reference
Loss of a metal-binding site in gelsolin leads to familial amyloidosis-Finnish type., Kazmirski SL, Isaacson RL, An C, Buckle A, Johnson CM, Daggett V, Fersht AR, Nat Struct Biol. 2002 Feb;9(2):112-6. PMID:11753432
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