Insights into the structural perturbations of spliced variants of CD44: a modeling and simulation approach

Abstract: Transient interactions between Cancer Stem cells (CSCs) and components of the tumor microenvironment initiate various signaling pathways crucial for carcinogenesis. Predominant hyaluronan (HA) receptor, CD44 is structurally and functionally one of the most variable cell surface receptors having the potential to generate a diverse repertory of CD44 isoforms by alternative splicing of variant exons and posttranslational modifications. A structurally distinctive variant of CD44, CD44v10 has an inevitable role in malignant progression, invasion and metastasis. This can be attributed to the binding of HA with CD44v10, which demonstrates a completely different behavioural pattern as compared to the other spliced variants of CD44 molecule. Absence of a comprehensively predicted crystal structure of human CD44s and CD44v10 is an impediment in understanding the resultant structural alterations caused by the binding of HA. Thus, in this study we aim to predict the CD44s & CD44v10 structures to their close...