NACA as a Potential Cellular Target of Hepatitis B Virus PreS1 Protein

Abstract

The mechanisms of the attachment and penetration of hepatitis B virus remain obscure. It has been demonstrated that the preS1 region is essential for viral assembly and infectivity, however, as its cellular receptor has still not been identified unequivocally, we used a yeast two-hybrid system to screen the cellular proteins that can interact with preS1 protein. The protein recovered from a human liver cDNA library was nascent polypeptide-associated complex alpha polypeptide. The interaction between preS1 and nascent polypeptide-associated complex alpha polypeptide was verified by mating experiment and coimmunoprecipitation of COS7 cell lysates expressing both proteins. Based on these results, we speculate that nascent polypeptide-associated complex alpha polypeptide is a functional target of hepatitis B virus preS1 protein in cells.

Crystal structures of NAC domains of human nascent polypeptide-associated complex (NAC) and its αNAC subunit

“…For example, αNAC can function as a transcription coactivator St-Arnaud, 1998;St-Arnaud and Quelo, 1998;Yotov et al, 1998); it is a positive regulator in human erythroid-cell differentiation (Lopez et al, 2005) and a negative regulator in the proliferation, differentiation, and cytotoxic activation of CD8 (+) T cells (Al-Shanti et al, 2004;Al-Shanti and Aldahoodi, 2006). Furthermore, αNAC can interact with several disease related proteins (Goatley et al, 2002;Mossabeb et al, 2002;Li et al, 2005;Mittermann et al, 2008). What does isolated αNAC look like?…”

Deciphering the mystery of hepatitis B virus receptors: A historical perspective

“…NACA also have sequence similarity with many transcription-regulating proteins [30].This similarity leads to some hypothetical deductions which are, NACA may be acting as a transcriptional coactivator enhancing the c-Jun/ c-Jun homodimer and c-Fos [42]. It might be interacting with the TATA box-binding protein and four-way DNA junction.…”

“…There are several examples of proteins that use same strategy and act as viral receptor. The localization of NACA provides evidence that it binds with preS1 of HBV and act as entry receptor [30].…”

“…It might be a merely possibility that for regulating the transcriptional function of preS1 NACA may act as a cellular protein and that its binding to preS1 may prevent interaction of NACA with other host proteins important for its function. The interaction between preS1 and NACA and the resulting pathophysiological significance is largely unknown [30].…”

“…The same HepG2 cells were later reported to carry human squamous cell carcinoma antigen 1 [11], a membrane protein, interacting with the same infamous residues preS1 21-47 amino acids [47]. The list gets populated by past studies reporting immunoglobulin A receptor [54], asialoglycoprotein receptor [67], hepatitis B virus binding factor [5], Glyceraldehyde 3 phosphate dehydrogenase [52], P80 [56], nascent polypeptide-associated complex a polypeptide (NACA) [30], GRP75 [7], lipoprotein lipase [70], heparin sulfate [57] and sodium taurocholate cotransporting polypeptide (NTCP) (Fig. 1).…”