α-Synuclein mutations cluster around a putative protein loop()

With the recent identification of two new pathogenic mutations in α-synuclein, we map the five known pathogenic mutations onto the best available models of the protein structure. We show that four of the five mutations map to a potential fold in the protein with the exception being the A30P mutation in which the substitution would be expected to have a profound effect on protein structure. We discuss this localisation in terms of the proposed mechanisms for mutation pathogenicity.