A Protean Clamp Guides Membrane Targeting of Tail-Anchored Proteins

To maintain cellular organization, many chaperones and targeting factors escort nascent proteins to membrane destinations. It was generally thought that substrate proteins preferably bind conformationally closed chaperones. However, how the nature and dynamics of the targeting complex help guide substrate proteins to the target membrane is not understood for most pathways. We addressed this question for the conserved ATPase Get3, which targets the essential class of tail-anchored proteins (TAs) to the endoplasmic reticulum (ER).