Human apolipoprotein A-I: structure determination and analysis of unusual diffraction characteristics

The crystallization and structure determination of recombinant human apolip oprotein A-I (apo A-I), the major protein component of high-density lipopro tein, is described. The fragment crystallized, residues 44-243 of native ap o A-I [apo Delta(1-43)A-I], is very similar to intact native apo A-I in its ability to bind lipid, to be incorporated into high-density lipoproteins a nd to activate lecithin-cholesterol acyl transferase. Apo Delta(1-43)A-I cr ystallizes from 1.0-1.4 M sodium citrate pH 6.5-7.5 in space group P2(1)2(1 )2(1), With unit-cell parameters a = 97.47, b = 113.87, c = 196.19 Angstrom (crystal form I). The crystals exhibit unusual diffraction intensity spike s and axial extinctions that are discussed in the context of the 4 Angstrom crystal structure. When flash-cooled to 100 K, the crystals diffract synch rotron radiation to 3 Angstrom resolution. Radiation sensitivity and crysta l-to-crystal variation have hindered the assembly of a complete 3 Angstrom data set.