This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1kcq
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1kcq.jpg|left|200px]] | + | [[Image:1kcq.jpg|left|200px]] |
| - | + | ||
| - | '''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== | ||
| Line 10: | Line 19: | ||
==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]] | ||
| Line 30: | Line 39: | ||
[[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
| |||||||
| , resolution 1.65Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| 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
Page seeded by OCA on Thu Mar 20 12:15:40 2008
