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Structural Study of Piezo Channel, a Unique Family of Eukaryotic Mechanosensitive Channel

Citation

Kamajaya, Aron (2017) Structural Study of Piezo Channel, a Unique Family of Eukaryotic Mechanosensitive Channel. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9JQ0Z00. http://resolver.caltech.edu/CaltechTHESIS:07182016-144756449

Abstract

Piezo is a unique family of eukaryotic mechanosensitive (MS) channel. With over 2500 amino acids per subunit, intact Piezo channel is one of the largest ion channels known to date. Two versions of Piezo can be found in vertebrates, namely PIEZO1 and PIEZO2. PIEZO1 appears to play roles in processes which control physiological homeostasis, whereas PIEZO2 assumes roles in mechanical somatosensation. A number of mutations mapped onto PIEZO1 or PIEZO2 are found in several hereditary human diseases, such as Dehydrated Hereditary Stomatocytosis, Gordon syndrome, and Distal Arthrogryposis. Although biochemical and functional studies provided many insightful findings, structural study of Piezo was very minimal. Herein, I described the structural investigation of Piezo channel. In the first study, we isolated a conserved soluble domain of Piezo (C-terminal loop 2, CTL2) from the C. elegans homolog, and provided the first molecular glimpse into this enigmatic MS channel. Subsequently, I described challenges that are associated with the expression and protein preparation of the full length Piezo channel. Recently, the full length mouse PIEZO1 structure solved by single particle cryo-EM revealed trimeric arrangement of the intact channel. CTL2 domain forms an extracellular cap which makes up the central core in this Piezo model. Lastly, we isolated a stable C-terminal fragment of Piezo. This fragment corresponds to the entire central core of Piezo channel and a few upstream transmembrane helices. This fragment can be localized to the plasma membrane. Further investigation is needed to look at the functionality of this fragment.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Piezo channel
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Biochemistry and Molecular Biophysics
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Rees, Douglas C.
Thesis Committee:
  • Lester, Henry A. (chair)
  • Clemons, William M.
  • Chan, David C.
  • Rees, Douglas C.
Defense Date:12 July 2016
Record Number:CaltechTHESIS:07182016-144756449
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:07182016-144756449
DOI:10.7907/Z9JQ0Z00
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.str.2014.08.009DOIArticle adapted for Chapter 2
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:9891
Collection:CaltechTHESIS
Deposited By: Aron Kamajaya
Deposited On:27 Jul 2016 16:20
Last Modified:27 Jul 2016 16:26

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