Research Papers: Pathology:

In silico predicted structural and functional insights of all missense mutations on 2B domain of K1/K10 causing genodermatoses

Santasree Banerjee, Qian Wu, Yuyi Ying, Yanni Li, Matsuyuki Shirota, Dante Neculai and Chen Li _

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Oncotarget. 2016; 7:52766-52780. https://doi.org/10.18632/oncotarget.10599

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Santasree Banerjee1,2, Qian Wu1, Yuyi Ying1, Yanni Li1, Matsuyuki Shirota3, Dante Neculai1 and Chen Li1

1 Department of Cell Biology and Medical Genetics, School of Medicine, Zhejiang University, Hangzhou, China

2 BGI-Shenzhen, Shenzhen, China

3 Department of Applied Information Sciences, Graduate School of Information Sciences, Tohoku University, Sendai, Japan

Correspondence to:

Chen Li, email:

Keywords: genodermatoses, missense mutations, coiled-coil heterodimer, in silico analysis, Pathology Section

Received: March 30, 2016 Accepted: May 17, 2016 Published: July 13, 2016


The K1 and K10 associated genodermatoses are characterized by clinical symptoms of mild to severe redness, blistering and hypertrophy of the skin. In this paper, we set out to computationally investigate the structural and functional effects of missense mutations on the 2B domain of K1/K10 heterodimer and its consequences in disease phenotype. We modeled the structure of the K1/K10 heterodimer based on crystal structures for the human homolog K5/K14 heterodimer, and identified that the missense mutations exert their effects on stability and assembly competence of the heterodimer by altering physico-chemical properties, interatomic interactions, and inter-residue atomic contacts. Comparative structural analysis between all the missense mutations and SNPs showed that the location and physico-chemical properties of the substituted amino acid are significantly correlated with phenotypic variations. In particular, we find evidence that a particular SNP (K10, p.E443K) is a pathogenic nsSNP which disrupts formation of the hydrophobic core and destabilizes the heterodimer through the loss of interatomic interactions. Our study is the first comprehensive report analyzing the mutations located on 2B domain of K1/K10 heterodimeric coiled-coil complex.

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