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. 2014 Oct:27:355-65.
doi: 10.1016/j.meegid.2014.07.022. Epub 2014 Aug 10.

In-silico analysis of claudin-5 reveals novel putative sites for post-translational modifications: Insights into potential molecular determinants of blood-brain barrier breach during HIV-1 infiltration

Faryal Mehwish Awan  1 , Sadia Anjum  2 , Ayesha Obaid  1 , Amjad Ali  1 , Rehan Zafar Paracha  1 , Hussnain Ahmed Janjua  3
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In-silico analysis of claudin-5 reveals novel putative sites for post-translational modifications: Insights into potential molecular determinants of blood-brain barrier breach during HIV-1 infiltration

Faryal Mehwish Awan et al. Infect Genet Evol. 2014 Oct.

Abstract

The blood-brain barrier (BBB) poses a huge challenge and is a serious issue in deciphering the pathophysiology of central nervous system disorders. Endothelial tight junctions play an essential role in maintaining the integrity of the BBB. Post-translational modifications (PTMs) in endothelial tight junction proteins are known to cause deleterious functional impairment and possible disruptions in BBB integrity. PTMs in tight junction proteins play an important role in human immunodeficiency virus type 1 (HIV-1) entry through the BBB. Human claudin-5 is one of the highly expressed brain endothelial tight junction protein and various PTMs in claudin-5 are expected to aid HIV-1 in crossing the BBB. A precise characterization of PTMs in claudin-5 is important for understanding its role in HIV-1 brain infiltration. In this study, we have examined post-translational crosstalk between phosphorylation, O-glycosylation, palmitoylation and methylation sites in claudin-5, which could alter claudin-5's ability to maintain BBB integrity. To the best of our knowledge, this is the first report on claudin-5 protein that suggests a novel interplay between potential PTM sites. PTMs of predicted residues in claudin-5, suggested in this study, can serve as compelling _targets for potential therapeutic agents against HIV-1 induced neuropathogenesis. Further site-specific experimental studies in this aspect are highly recommended.

Keywords: Blood–brain barrier; Brain endothelial cells; HIV-1; Post-translational modifications in claudin-5; Tight junctions.

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