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Article

Structural Characterization of the CD44 Stem Region for Standard and Cancer-Associated Isoforms

1
Department of Engineering Science and Ocean Engineering, National Taiwan University, Taipei 10617, Taiwan
2
Department of Civil Engineering, National Taiwan University, Taipei 10617, Taiwan
3
Department and Graduate Institute of Pharmacology, National Taiwan University, Taipei 10617, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(1), 336; https://doi.org/10.3390/ijms21010336
Received: 7 November 2019 / Revised: 26 December 2019 / Accepted: 31 December 2019 / Published: 3 January 2020
(This article belongs to the Collection Computational Studies of Biomolecules)
CD44 is widely expressed in most vertebrate cells, whereas the expression of CD44v6 is restricted to only a few tissues and has been considered to be associated with tumor progression and metastasis. Thus, CD44v6 has been recognized as a promising prognostic biomarker and therapeutic target for various cancers for more than a decade. However, despite many experimental studies, the structural dynamics and differences between CD44s and CD44v6, particularly in their stem region, still remain elusive. Here, a computational study was conducted to address these problems. We found that the stem of CD44s adopted predominantly two conformations, one featuring antiparallel β-sheets and the other featuring parallel β-sheets, whereas the stem of CD44v6 adopted mainly one conformation with relatively highly suppressed β-sheet contents. Moreover, Phe215 was found to be essential in the β-sheets of both CD44s and CD44v6. We finally found intramolecular Phe215–Trp224 hydrogen-bonding interactions and hydrophobic interactions with Phe215 that cooperatively drove conformational differences upon the addition of the v6 region to CD44. Our study elucidated the structural differences between the stem regions of CD44s and CD44v6 and thus can offer useful structural information for drug design to specifically target CD44v6 in promising clinical applications. View Full-Text
Keywords: CD44; CD44v6; receptor tyrosine kinase (RTK); metastasis; tumor progression; β-sheets; molecular dynamics simulations CD44; CD44v6; receptor tyrosine kinase (RTK); metastasis; tumor progression; β-sheets; molecular dynamics simulations
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MDPI and ACS Style

Chen, K.-L.; Li, D.; Lu, T.-X.; Chang, S.-W. Structural Characterization of the CD44 Stem Region for Standard and Cancer-Associated Isoforms. Int. J. Mol. Sci. 2020, 21, 336. https://doi.org/10.3390/ijms21010336

AMA Style

Chen K-L, Li D, Lu T-X, Chang S-W. Structural Characterization of the CD44 Stem Region for Standard and Cancer-Associated Isoforms. International Journal of Molecular Sciences. 2020; 21(1):336. https://doi.org/10.3390/ijms21010336

Chicago/Turabian Style

Chen, Kun-Lin, Deng Li, Ting-Xuan Lu, and Shu-Wei Chang. 2020. "Structural Characterization of the CD44 Stem Region for Standard and Cancer-Associated Isoforms" International Journal of Molecular Sciences 21, no. 1: 336. https://doi.org/10.3390/ijms21010336

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