tetano
Editor, Senior Moderator
Protein Sci. 2013 Feb 7. doi: 10.1002/pro.2232. [Epub ahead of print]
Modeling the membrane environmenthas implications for membrane protein structureand function: Influenza a M2 protein.
Zhou HX, Cross TA.
Source
Department of Physics, Florida State University, Tallahassee, Florida, 32306; Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida, 32306; National High Magnetic Field Laboratory, Florida State University, Tallahassee, Florida, 32306.
Abstract
The M2 protein, a proton channel, from Influenza A has been structurally characterized by X-ray diffraction and by solution and solid-state NMR spectroscopy in a variety of membrane mimetic environments. These structures show substantial backbone differences even though they all present a left-handed tetramerichelical bundle for the transmembrane domain. Variations in the helix tilt influence drug binding and the chemistry of the histidine tetrad responsible for acid activation, proton selectivity and transport. Some of the major structural differences do not arise from the lack of precision, but instead can be traced to theinfluences of the membrane mimetic environments. The structure in lipid bilayers displays unique chemistry for the histidine tetrad, which binds two protons cooperatively to form a pair of imidazole-imidazolium dimers. The resulting inter-histidine hydrogen bonds contribute to a three orders of magnitude enhancement in tetramer stability. Integration with computation has provided detailedunderstanding of the functional mechanism for proton selectivity, conductance and gating of this important drug target.
Copyright ? 2013 The Protein Society.
PMID:
23389890
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23389890
Modeling the membrane environmenthas implications for membrane protein structureand function: Influenza a M2 protein.
Zhou HX, Cross TA.
Source
Department of Physics, Florida State University, Tallahassee, Florida, 32306; Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida, 32306; National High Magnetic Field Laboratory, Florida State University, Tallahassee, Florida, 32306.
Abstract
The M2 protein, a proton channel, from Influenza A has been structurally characterized by X-ray diffraction and by solution and solid-state NMR spectroscopy in a variety of membrane mimetic environments. These structures show substantial backbone differences even though they all present a left-handed tetramerichelical bundle for the transmembrane domain. Variations in the helix tilt influence drug binding and the chemistry of the histidine tetrad responsible for acid activation, proton selectivity and transport. Some of the major structural differences do not arise from the lack of precision, but instead can be traced to theinfluences of the membrane mimetic environments. The structure in lipid bilayers displays unique chemistry for the histidine tetrad, which binds two protons cooperatively to form a pair of imidazole-imidazolium dimers. The resulting inter-histidine hydrogen bonds contribute to a three orders of magnitude enhancement in tetramer stability. Integration with computation has provided detailedunderstanding of the functional mechanism for proton selectivity, conductance and gating of this important drug target.
Copyright ? 2013 The Protein Society.
PMID:
23389890
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23389890