1g96

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models 1g96, resolution 2.5Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

HUMAN CYSTATIN C; DIMERIC FORM WITH 3D DOMAIN SWAPPING

Overview

The crystal structure of human cystatin C, a protein with amyloidogenic, properties and a potent inhibitor of cysteine proteases, reveals how the, protein refolds to produce very tight two-fold symmetric dimers while, retaining the secondary structure of the monomeric form. The dimerization, occurs through three-dimensional domain swapping, a mechanism for forming, oligomeric proteins. The reconstituted monomer-like domains are similar to, chicken cystatin except for one inhibitory loop that unfolds to form the, 'open interface' of the dimer. The structure explains the tendency of, human cystatin C to dimerize and suggests a mechanism for its aggregation, in the brain arteries of elderly people with amyloid angiopathy. A more, severe 'conformational disease' is associated with the L68Q mutant of, human cystatin C, which causes massive amyloidosis, cerebral hemorrhage, and death in young adults. The structure of the three-dimensional, domain-swapped dimers shows how the L68Q mutation destabilizes the, monomers and makes the partially unfolded intermediate less unstable., Higher aggregates may arise through the three-dimensional domain-swapping, mechanism occurring in an open-ended fashion in which partially unfolded, molecules are linked into infinite chains.

About this Structure

1G96 is a Single protein structure of sequence from Homo sapiens with CL and GOL as ligands. Full crystallographic information is available from OCA.

Reference

Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping., Janowski R, Kozak M, Jankowska E, Grzonka Z, Grubb A, Abrahamson M, Jaskolski M, Nat Struct Biol. 2001 Apr;8(4):316-20. PMID:11276250

Page seeded by OCA on Mon Nov 12 17:01:55 2007