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Full text release has been delayed at the author's request until December 21, 2025

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Elucidating the Structure of Cadherin-23 Repeats Essential for Hearing

Avila-Estrada, Jeshua Kennedy
http://rave.ohiolink.edu/etdc/view?acc_num=osu159821802977914

Abstract Details

2020, Master of Science, Ohio State University, Chemistry.
Inner-ear mechanotransduction is a process where stimuli from sound or head movements are converted into electrical signals. To better understand the mechanisms behind mechanotransduction, understanding the properties of the mechanotransduction apparatus is crucial. The tip-link filament is a component of the inner-ear mechanotransduction apparatus essential to hearing and is composed of two proteins: Cadherin-23 (CDH23) and protocadherin-15 (PCDH15). CDH23 makes up the majority of the tip link and is composed of 27 extracellular cadherin (EC) repeats that are approximately 100 amino acids in length. CDH23 is thought to form a parallel cis dimer that interacts tip-to-tip with PCDH15. There are over 100 missense mutations known to cause deafness that occur on the CDH23 EC repeats. The molecular mechanisms underlying deafness have yet to be fully elucidated, and the structure of several EC repeats are still unknown, with research focused on uncovering the structures of these missing repeats. Here I describe experiments dedicated to the expression, purification, and refolding of specific EC repeats, including protein fragments: Mus musculus (mm) CDH23 EC3-4, mm CDH23 EC5-6, mm CDH23 EC11-12, and Homo sapiens (hs) CDH23 EC18-19. Mutations were conducted on the EC11-12 fragment to understand the effects of a cysteine disulfide bond on cis dimer interactions. We successfully expressed, purified, and refolded these proteins, and crystal screens were set up for hs CDH23 EC18-19. These are the first steps toward solving the x-ray crystal structure of hs CDH23 EC18-19 and towards solving the structure of the entire CDH23 ectodomain.
Marcos Sotomayor (Advisor)
Thomas Magliery (Committee Member)
51 p.
Biochemistry; Chemistry
Cadherin; Protein Refolding; Biochemistry; Chemistry

Recommended Citations

Citations

  • Avila-Estrada, J. K. (2020). Elucidating the Structure of Cadherin-23 Repeats Essential for Hearing [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu159821802977914

    APA Style (7th edition)

  • Avila-Estrada, Jeshua. Elucidating the Structure of Cadherin-23 Repeats Essential for Hearing. 2020. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu159821802977914.

    MLA Style (8th edition)

  • Avila-Estrada, Jeshua. "Elucidating the Structure of Cadherin-23 Repeats Essential for Hearing." Master's thesis, Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu159821802977914

    Chicago Manual of Style (17th edition)

osu159821802977914
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This open access ETD is published by The Ohio State University and OhioLINK.