Structural effects of fibulin 5 missense mutations associated with age-related macular degeneration and cutis laxa.

ABSTRACT:

Purpose

AMD has a complex etiology with environmental and genetic risk factors. Ten fibulin 5 sequence variants have been associated with AMD and two other fibulin 5 mutations cause autosomal-recessive cutis laxa. Fibulin 5 is a 52-kDa calcium-binding epidermal growth factor (cbEGF)-rich extracellular matrix protein that is essential for the formation of elastic tissues. Biophysical techniques were used to detect structural changes in the fibulin 5 mutants and to determine whether changes are predictive of pathogenicity.

Methods

Native PAGE, nonreduced SDS-PAGE, size-exclusion column multiangle laser light scattering, sedimentation velocity, and circular dichroism (CD) were used to investigate the mobility, hydrodynamic radii, folding, and oligomeric states of the fibulin 5

SUBMITTER: Jones RP 

PROVIDER: S-EPMC2868478 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature