Mutation mapping of apolipoprotein A-I structure assisted with the putative cholesterol recognition regions》.pdf

Biochimica et Biophysica Acta 1834 (2013) 2030–2035 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: /locate/bbapap Mutation mapping of apolipoprotein A-I structure assisted with the putative cholesterol recognition regions Alexander D. Dergunov ⁎ National Research Centre for Preventive Medicine, 10, Petroverigsky Street, 101990 Moscow, Russia a r t i c l e i n f o a b s t r a c t Article history: Twenty-nine from 52 missense mutations in apoA-I gene are predicted to be deleterious by both SIFT and Received 2 April 2013 PolyPhen-2 algorithms. Among those, eight mutations with a prominent change in structure stability as Received in revised form 4 June 2013 modeled by the SDM tool for both lipid-free (Mei and Atkinson (2011) PDB ID: 3R2P) and HDL-bound Accepted 15 June 2013 (Wu et al. (2009) PDB ID: 3K2S) apoA-I, are referred as structural. The remaining mutations with a preferen- Available online 24 June 2013 tial location in a long intrinsically disordered region, predicted by the SPINE-D and DNdisorder tools, may in- fluence the functional sites. Among structural mutations, five amyloidosis-only-related mutations, significant Keywords: Missense mutation in a lipid-free structure, are located in 1–90 region. Six amyloidosis- and hypoalphalipoproteinemia- Apolipoprotein A-I