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Novel Roles of the SRP RNA in Co-Translational Protein Targeting


Shen, Kuang (2013) Novel Roles of the SRP RNA in Co-Translational Protein Targeting. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/NWWW-0867.


The signal recognition particle (SRP) and its receptor (SR) are universally conserved protein machineries that deliver nascent peptides to their proper destination. The SRP RNA is a universally conserved and essential component of SRP, which serves as the “catalyst” of the protein targeting cycle. The SRP RNA accelerates SRP-SR complex formation at the beginning of the protein targeting reaction, and triggers GTP hydrolysis and SRP-SR complex disassembly at the end. Here we combined biochemical and biophysical approaches to investigate the molecular mechanism of the functions of the SRP RNA. We found that two functional ends in the SRP RNA mediate distinct functions. The tetraloop end facilitates initial assembly of SRP and SR by mediating an electrostatic interaction with the Lys399 receptor, which ensures efficient and accurate substrate targeting. At the later stage of the SRP cycle, the SRP-SR complex relocalizes ~ 100 Angstrom to the 5’,3’-distal end of the RNA, a conformation crucial for GTPase activation and cargo handover. These results, combined with recent structural work, elucidate the functions of the SRP RNA during the protein targeting reaction.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Signal recognition particle, SRP RNA, single molecule, protein-nucleotide interaction
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Awards:The Herbert Newby McCoy Award, 2013.
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Shan, Shu-ou
Thesis Committee:
  • Rees, Douglas C. (chair)
  • Gray, Harry B.
  • Campbell, Judith L.
  • Shan, Shu-ou
Defense Date:7 May 2013
Non-Caltech Author Email:shenk0128 (AT)
Record Number:CaltechTHESIS:05292013-215935625
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:7768
Deposited By: Kuang Shen
Deposited On:03 Jun 2013 20:56
Last Modified:04 Oct 2019 00:01

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