Proteins Nitrated At Specific Sites

Researchers have developed the first synthetic method to substitute nitrated versions of tyrosine at specific sites in otherwise native proteins. They used the technique to study the effects of replacing tyrosine with 3-nitrotyrosine in α-synuclein, which aggregates to form fibrils in the brains of Parkinson’s disease patients. α-Synuclein has four tyrosines, and nitration of some of them may help lead to neurodegeneration by promoting fibril formation. Existing techniques to control tyrosine nitration have limited specificity, making it difficult to study such phenomena. Hilal A. Lashuel and coworkers at ETH Lausanne reported using solid-phase peptide synthesis, native chemical ligation, and a new desulfurization technique to nitrate one or more tyrosines in α-synuclein site-specifically (J. Am. Chem. Soc. 2015, DOI: 10.1021/ja5131726). This enabled them to study the effects of tyrosine nitration on α-synuclein structure, oligomerization, and fibril formation. The approach also will facilitate the development of antibodies and imaging agents to detect and quantify α-synuclein species that form aggregates in the brains of Parkinson’s patients, Lashuel said.