Research Project: Türdeş Olmayan Sistemlerde Uyarlanabilir Çözünürlük Simülasyon Yönteminin Geliştirilmesi
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Contributors
Funders
ID
TB.00556
Authors
Sayar, Mehmet
Faculty Member
Publications
Modeling adsorption, conformation, and orientation of the Fis1 tail anchor at the mitochondrial outer membrane
(MDPI, 2022) Özgür, Beytullah; Sayar, Mehmet; Dunn, Cory D.; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; Yes; College of Engineering; GRADUATE SCHOOL OF SCIENCES AND ENGINEERING
Proteins can be targeted to organellar membranes by using a tail anchor (TA), a stretch of hydrophobic amino acids found at the polypeptide carboxyl-terminus. The Fis1 protein (Fis1p), which promotes mitochondrial and peroxisomal division in the yeast Saccharomyces cerevisiae, is targeted to those organelles by its TA. Substantial evidence suggests that Fis1p insertion into the mitochondrial outer membrane can occur without the need for a translocation machinery. However, recent findings raise the possibility that Fis1p insertion into mitochondria might be promoted by a proteinaceous complex. Here, we have performed atomistic and coarse-grained molecular dynamics simulations to analyze the adsorption, conformation, and orientation of the Fis1(TA). Our results support stable insertion at the mitochondrial outer membrane in a monotopic, rather than a bitopic (transmembrane), configuration. Once inserted in the monotopic orientation, unassisted transition to the bitopic orientation is expected to be blocked by the highly charged nature of the TA carboxyl-terminus and by the Fis1p cytosolic domain. Our results are consistent with a model in which Fis1p does not require a translocation machinery for insertion at mitochondria.
