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1.A.32 The Type B Influenza Virus NB Channel (NB-C) Family

The mechanisms and functions of viral channel proteins have been reviewed by Fischer and Hsu (2011) and Fischer et al. (2012). The 100 residue integral membrane NB glycoprotein of influenza virus type B forms voltage-independent ion channels. It consists of an N-terminal extracellular 20 residue domain, a single 20 residue TMS, and a C-terminal cytoplasmic 60 residue domain. It is present in the membranes of virus-infected cells. In these respects, it resembles the Matrix-2 channel peptides of influenza virus type A (TC# 1.A.19), but the NB and M2 channel proteins exhibit no perceptible sequence similarity. The TMS of NB displays ser-4, thr-8, and ser-12 on the same side of the putative helix with most other residues being hydrophobic. This is not a characteristic of M2. Moreover, M2 is a proton-conducting channel while NB is a general ion-conducting channel. Thus, although M2 and NB may possibly be distant homologues (based on similar sizes, typologies and channel-like functions), homology cannot be demonstrated. These two systems are therefore assigned to different families.

At neutral pH, NB channels are more permeable to Na+ than Cl- (PNa+/PCl- @ 10 at pH 6.5), but at pH 2.5, the permeability to Cl- is four-fold higher than that to Na+. NB induces a Na+-dependent H+ current and a pH-activated Cl- current. Conductance is concentration-dependent with multiple conductance levels, probably corresponding to different oligomerization states: n = 4 , 5 and 6.

The generalized transport reaction catalyzed by the NB channel is:

Ions (in) ions (out)

References associated with 1.A.32 family:

Fischer, W.B. and H.J. Hsu. (2011). Viral channel forming proteins - modeling the target. Biochim. Biophys. Acta. 1808: 561-571. 20546700
Fischer, W.B. and M.S. Sansom. (2002). Viral ion channels: structure and function. Biochim. Biophys. Acta 1561: 27-45. 11988179
Fischer, W.B., M. Pitkeathly, B.A. Wallace, L.R. Forrest, G.R. Smith, and M.S. Sansom. (2000). Transmembrane peptide NB of influenza B: a simulation, structure, and conductance study. Biochemistry 41: 12708-12716. 11027151
Fischer, W.B., Y.T. Wang, C. Schindler, and C.P. Chen. (2012). Mechanism of function of viral channel proteins and implications for drug development. Int Rev Cell Mol Biol 294: 259-321. 22364876