Abstract:
:The heart of the H+ conductance mechanism in the homotetrameric M2 H+ channel from influenza A is a set of four histidine side chains. Here, we show that protonation of the third of these imidazoles coincides with acid activation of this transmembrane channel and that, at physiological pH, the channel is closed by two imidazole-imidazolium dimers, each sharing a low-barrier hydrogen bond. This unique construct succeeds in distributing a pair of charges over four rings and many atoms in a low dielectric environment to minimize charge repulsion. These dimers form with identical pKas of 8.2 +/- 0.2, suggesting cooperative H+ binding and clearly illustrating high H+ affinity for this channel. The protonation behavior of the histidine side chains has been characterized by using solid-state NMR spectroscopy on the M2 transmembrane domain in fully hydrated lipid bilayers where the tetrameric backbone structure is known. Furthermore, electrophysiological measurements of multichannel and single-channel experiments confirm that these protein constructs are functional.
journal_name
Proc Natl Acad Sci U S Aauthors
Hu J,Fu R,Nishimura K,Zhang L,Zhou HX,Busath DD,Vijayvergiya V,Cross TAdoi
10.1073/pnas.0601944103subject
Has Abstractpub_date
2006-05-02 00:00:00pages
6865-70issue
18eissn
0027-8424issn
1091-6490pii
0601944103journal_volume
103pub_type
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