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Molecular Mechanism of the Strong Cell-Adhesion by Cadherin-23

66 Pages Posted: 11 Apr 2018 Sneak Peek Status: Review Complete

See all articles by G. S. Singaraju

G. S. Singaraju

Indian Institute of Science Education and Research (IISER) - Department of Chemical Sciences

A. Sagar

Indian Institute of Science Education and Research (IISER) - Department of Chemical Sciences

A. Kumar

Indian Institute of Science Education and Research (IISER) - Department of Physical Sciences

J. S. Samuel

Indian Institute of Science Education and Research (IISER) - Department of Chemical Sciences

J. P. Hazra

Indian Institute of Science Education and Research (IISER) - Department of Chemical Sciences

M. K. Sannigrahi

Indian Institute of Science Education and Research (IISER) - Department of Chemical Sciences

R. M. Yennamalli

Indian Institute of Science Education and Research (IISER) - Department of Physical Sciences

Ashish

CSIR-Institute of Microbial Technology

S. Rakshit

Indian Institute of Science Education and Research (IISER) - Department of Chemical Sciences

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Abstract

Cadherin-23, a giant non-classical cadherin, has a stronger cell-aggregating index compared to classical E-cadherin and possesses the ability to sort cells on the basis of the classes of cadherins. These phenomena overall indicated a different antiparallel-binding interface of the Cadherin-23 homodimer from classical-cadherins. Combining biochemical, biophysical, and computational methodologies, we generated a model of the homodimer, and confirmed by mutational modifications. The dimer consists of two electrostatic-based interfaces extended up to two terminal domains. This is atypical to classical-cadherins, and favors high cell-aggregating propensity. We quantified the strength of the dimer using single-molecule force spectroscopy, and measured significantly low off-rate(~8x10-4s-1). We identified a point-mutation, E78K, that disrupts this binding. Interestingly similar mutation at the binding interface was identified in skin-cancer, supporting the physiological relevance of the interface. Overall, this novel structural basis of the strong Cadherin-23 adhesion may have far-reaching applications in the fields of mechanobiology and cancer.

Suggested Citation

Singaraju, G. S. and Sagar, A. and Kumar, A. and Samuel, J. S. and Hazra, J. P. and Sannigrahi, M. K. and Yennamalli, R. M. and , Ashish and Rakshit, S., Molecular Mechanism of the Strong Cell-Adhesion by Cadherin-23 (2018). Available at SSRN: https://ssrn.com/abstract=3155734 or http://dx.doi.org/10.2139/ssrn.3155734
This is a paper under consideration at Cell Press and has not been peer-reviewed.

G. S. Singaraju

Indian Institute of Science Education and Research (IISER) - Department of Chemical Sciences

Thriuvananthapuram
India

A. Sagar

Indian Institute of Science Education and Research (IISER) - Department of Chemical Sciences

Thriuvananthapuram
India

A. Kumar

Indian Institute of Science Education and Research (IISER) - Department of Physical Sciences

Thriuvananthapuram
India

J. S. Samuel

Indian Institute of Science Education and Research (IISER) - Department of Chemical Sciences

Thriuvananthapuram
India

J. P. Hazra

Indian Institute of Science Education and Research (IISER) - Department of Chemical Sciences

Thriuvananthapuram
India

M. K. Sannigrahi

Indian Institute of Science Education and Research (IISER) - Department of Chemical Sciences

Thriuvananthapuram
India

R. M. Yennamalli

Indian Institute of Science Education and Research (IISER) - Department of Physical Sciences

Thriuvananthapuram
India

Ashish (Contact Author)

CSIR-Institute of Microbial Technology ( email )

Sector 39 A
Chandigarh, 160036
India

S. Rakshit

Indian Institute of Science Education and Research (IISER) - Department of Chemical Sciences

Thriuvananthapuram
India

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