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Mechanisms of Co-Translational Protein Targeting by Mammalian SRP


Lee, Jae Ho (2019) Mechanisms of Co-Translational Protein Targeting by Mammalian SRP. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/RF8Y-DK59.


Proper biogenesis of nascent protein is essential for cell survival. Signal recognition particle (SRP) is an essential and universally conserved factor involved in biogenesis of ~30% of the proteome through co-translational targeting of nascent proteins to Endoplasmic Reticulum (ER). Despite its importance, the mechanisms by which eukaryotic SRP ensure selective and efficient delivery of substrates to ER is poorly understood. Here, we reconstituted human SRP and SRP receptor (SR) to study the interaction between human SRP and SR, and conformational dynamics of SRP and SRP-SR targeting complex through biochemical and biophysical methods. We find that signal sequence and ribosomal components of the substrate sequentially activate human SRP. Especially, presence of signal sequence pre-organizes SRP conformation for efficient recruitment of SR, allowing specific and efficient targeting. In addition, we discover two essential roles of a conformational change in SR, where it is required not only for brining targeting complex near the ER membrane, but also for inducing subsequent conformational changes of SRP-SR complex that ensures proper delivery of substrates to Sec61 translocon on ER membrane.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Protein targeting, chaperones, signal recognition particle, GTPases, single-molecule spectroscopy, protein dynamics
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Shan, Shu-ou
Thesis Committee:
  • Hoelz, Andre (chair)
  • Rees, Douglas C.
  • Clemons, William M.
  • Shan, Shu-ou
Defense Date:22 May 2019
Funding AgencyGrant Number
Record Number:CaltechTHESIS:05292019-142906583
Persistent URL:
Related URLs:
URLURL TypeDescription adapted for Chapter 1. of this article was adapted for a section in Chapter 2.
Lee, Jae Ho0000-0002-8663-3209
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:11561
Deposited By: Jae Ho Lee
Deposited On:11 Jun 2019 18:55
Last Modified:04 Oct 2019 00:25

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