ALS-causing mutations in profilin-1 alter its conformational dynamics: A computational approach to explain propensity for aggregation

Exploring foci of: Scientific Reports • Vol 8 • No 1 ALS-causing mutations in profilin-1 alter its conformational dynamics: A computational approach to explain propensity for aggregation August 2018 • Mahmoud Kiaei, Meenakshisundaram Balasubramaniam, Vivek Govind Kumar, Robert J. Shmookler Reis, Mahmoud Moradi, Kottayil I. Varughese Abstract Profilin-1 (PFN1) is a 140-amino-acid protein with two distinct binding sites―one for actin and one for poly-L-proline (PLP). The best-described function of PFN1 is to catalyze actin elongation and polymerization. Thus far, eight DNA mutations in the PFN1 gene encoding the PFN1 protein are associated with human amyotrophic lateral sclerosis (ALS). We and others recently showed that two of these mutations (Gly118Val or G118V and Cys71Gly or C71G) cause ALS in rodents. In vitro studies suggested that Met114… Open Article Page

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