Predicting the targeting of tail-anchored proteins to subcellular compartments in mammalian cells

• DOI: 10.1242/jcs.200204
• Publication Date: 2017-03-22T00:40:23Z
• Authors: Joseph L. Costello; Inês G. Castro; Fátima Camões; Tina A. Schrader; Doug McNeall; Jing Yang; Evdokia-Anastasia...; Sílvia Gomes; Vivian Pogenberg; Nina A. Bonekamp; Daniela Ribeiro; Matthias Wilmanns; Gregory Jedd; Markus Islinger; Michael Schrader
• Keywords: Organelle; Peroxisomal targeting signal; Organelle biogenesis

Tail-anchored (TA) proteins contain a single transmembrane domain (TMD) at the C-terminus that anchors them to membranes of organelles where they mediate critical cellular processes. Accordingly, mutations in genes encoding TA have been identified number severe inherited disorders. Despite importance correctly targeting protein its appropriate membrane, mechanisms and signals involved are not fully understood. In this study, we identify additional peroxisomal proteins, discover more present on multiple organelles, reveal combination TMD hydrophobicity tail charge determines distinct organelle locations mammals. Specifically, an increase can override hydrophobic signal re-direct from ER peroxisomes or mitochondria vice versa. We show subtle changes those parameters shift between explaining why many same proteins. This enabled us associate characteristic physicochemical with particular groups. Using classification allowed successful prediction location uncharacterized for first time.