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The Get3 ATPase Drives Unidirectional Targeting of Tail-Anchored Membrane Proteins


Rome, Michael Evan (2014) The Get3 ATPase Drives Unidirectional Targeting of Tail-Anchored Membrane Proteins. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9DZ068N.


Efficient and accurate localization of membrane proteins is essential to all cells and requires a complex cascade of interactions between protein machineries. This is exemplified in the recently discovered Guided Entry of Tail-anchored protein pathway, in which the central targeting factor Get3 must sequentially interact with three distinct binding partners (Get4, Get1 and Get2) to ensure the targeted delivery of Tail-anchored proteins to the endoplasmic reticulum membrane. To understand the molecular and energetic principles that provide the vectorial driving force of these interactions, we used a quantitative fluorescence approach combined with mechanistic enzymology to monitor the effector interactions of Get3 at each stage of Tail-anchored protein targeting. We show that nucleotide and membrane protein substrate generate a gradient of interaction energies that drive the cyclic and ordered transit of Get3 from Get4 to Get2 and lastly to Get1. These data also define how the Get3/Tail-anchored complex is captured, handed over, and disassembled by the Get1/2 receptor at the membrane, and reveal a novel role for Get4/5 in recycling Get3 from the endoplasmic reticulum membrane at the end of the targeting reaction. These results provide general insights into how complex cascades of protein interactions are coordinated and coupled to energy inputs in biological systems.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Get3 ; ATPase ; membrane ; protein targeting
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Biology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Shan, Shu-ou
Thesis Committee:
  • Chan, David C. (chair)
  • Clemons, William M.
  • Campbell, Judith L.
  • Bjorkman, Pamela J.
  • Shan, Shu-ou
Defense Date:15 April 2014
Non-Caltech Author Email:michaelrome123 (AT)
Funding AgencyGrant Number
National Science Foundation Graduate Research FellowshipUNSPECIFIED
Record Number:CaltechTHESIS:04162014-173759568
Persistent URL:
Related URLs:
URLURL TypeDescription DOIArticle adapted for ch. 2
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8191
Deposited By: Michael Rome
Deposited On:28 Apr 2014 21:59
Last Modified:04 Oct 2019 00:04

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