Legler Patricia M, Brey Robert N, Smallshaw Joan E, Vitetta Ellen S, Millard Charles B
Naval Research Laboratories, Washington, DC 20375, USA.
Acta Crystallogr D Biol Crystallogr. 2011 Sep;67(Pt 9):826-30. doi: 10.1107/S0907444911026771. Epub 2011 Aug 9.
RiVax is a recombinant protein that is currently under clinical development as part of a human vaccine to protect against ricin poisoning. RiVax includes ricin A-chain (RTA) residues 1-267 with two intentional amino-acid substitutions, V76M and Y80A, aimed at reducing toxicity. Here, the crystal structure of RiVax was solved to 2.1 Å resolution and it was shown that it is superposable with that of the ricin toxin A-chain from Ricinus communis with a root-mean-square deviation of 0.6 Å over 258 C(α) atoms. The RiVax structure is also compared with the recently determined structure of another potential ricin-vaccine immunogen, RTA 1-33/44-198 R48C/T77C. Finally, the locations and solvent-exposure of two toxin-neutralizing B-cell epitopes were examined and it was found that these epitopes are within or near regions predicted to be involved in catalysis. The results demonstrate the composition of the RiVax clinical material and will guide ongoing protein-engineering strategies to develop improved immunogens.
RiVax是一种重组蛋白，目前正处于临床开发阶段，作为一种预防蓖麻毒素中毒的人用疫苗的一部分。RiVax包含蓖麻毒素A链（RTA）的1至267位残基，并带有两个有意引入的氨基酸替换，即V76M和Y80A，旨在降低毒性。在此，RiVax的晶体结构解析到了2.1 Å的分辨率，结果表明它与蓖麻籽蓖麻毒素A链的晶体结构可叠加，在258个C(α)原子上的均方根偏差为0.6 Å。还将RiVax的结构与另一种潜在的蓖麻毒素疫苗免疫原RTA 1 - 33/44 - 198 R48C/T77C最近确定的结构进行了比较。最后，研究了两个毒素中和性B细胞表位的位置和溶剂暴露情况，发现这些表位位于预计参与催化作用的区域内或附近。这些结果证明了RiVax临床材料的组成，并将指导正在进行的蛋白质工程策略，以开发改进的免疫原。
