1kcq
From Proteopedia
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| - | [[Image:1kcq.jpg|left|200px]] | + | [[Image:1kcq.jpg|left|200px]] |
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| - | '''Human Gelsolin Domain 2 with a Cd2+ bound''' | + | {{Structure |
| + | |PDB= 1kcq |SIZE=350|CAPTION= <scene name='initialview01'>1kcq</scene>, resolution 1.65Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=CD:CADMIUM ION'>CD</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''Human Gelsolin Domain 2 with a Cd2+ bound''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1KCQ is a [ | + | 1KCQ is a [[Single protein]] structure of 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=1KCQ OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/11753432 11753432] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: metal binding]] | [[Category: metal binding]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:15:40 2008'' |
Revision as of 10:15, 20 March 2008
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| , resolution 1.65Å | |||||||
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human Gelsolin Domain 2 with a Cd2+ bound
Contents |
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. 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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