Msp1 Is a Membrane Protein Dislocase for Tail-Anchored Proteins

The AAA protein Msp1 mediates clearance of excess tail-anchored proteins from the peroxisomal membrane

Msp1 is a conserved AAA ATPase in budding yeast localized to mitochondria where it prevents accumulation of mistargeted tail-anchored (TA) proteins, including the peroxisomal TA protein Pex15. Msp1 also resides on peroxisomes but it remains unknown how native TA proteins on mitochondria and peroxisomes evade Msp1 surveillance. We used live-cell quantitative cell microscopy tools and drug-induci...

Title: The AAA Protein Msp1 Mediates Clearance of Excess Tail-Anchored Proteins from the Peroxisomal Membrane

A conserved archaeal pathway for tail-anchored membrane protein insertion.

Eukaryotic tail-anchored (TA) membrane proteins are inserted into the endoplasmic reticulum by a post-translational TRC40 pathway, but no comparable pathway is known in other domains of life. The crystal structure of an archaebacterial TRC40 sequence homolog bound to ADP•AlF(4) (-) reveals characteristic features of eukaryotic TRC40, including a zinc-mediated dimer and a large hydrophobic groov...

A protean clamp guides membrane targeting of tail-anchored proteins.

Proper localization of proteins to target membranes is a fundamental cellular process. How the nature and dynamics of the targeting complex help guide substrate proteins to the target membrane is not understood for most pathways. Here, we address this question for the conserved ATPase guided entry of tail-anchored protein 3 (Get3), which targets the essential class of tail-anchored proteins (TA...

The conserved AAA-ATPase Msp1 confers organelle specificity to tail-anchored proteins.

The accuracy of tail-anchored (TA) protein targeting to the endoplasmic reticulum (ER) depends on the Guided Entry of Tail-Anchored (Get) protein targeting machinery. The fate of TA proteins that become inappropriately inserted into other organelles, such as mitochondria, is unknown. Here, we identify Msp1, a conserved, membrane-anchored AAA-ATPase (ATPase associated with a variety of cellular ...