Rice University

Department of Biochemistry and Cell Biology

Kevin R. MacKenzie

Laboratory Members




Structure, stability and folding of
integral membrane proteins

The goal of my laboratory is to understand transmembrane helix associations that underlie biological processes such as signal transduction.  Different aspects of membrane protein folding will be explored using methods ranging from genetic selection to molecular biophysics.

Although integral membrane proteins comprise perhaps 30% of open reading frames in genomes, they represent fewer than 1% of the entries in the Protein Data Bank.  Efforts in the lab are focused on identifying biologically important transmembrane domain interactions that are amenable to biophysical and biochemical analysis; T cell signaling is one area of interest.  Structures of complexes of a-helices determined by solution NMR will reveal the types of interactions that stabilize such oligomers.  Qualitative and quantitative measures of helix-helix association constants will be obtained using in vivo and in vitro assays.  Mutagenesis experiments will test the sequence dependence of these interactions.  A similar approach has led to a model for the dimerization of the transmembrane domain of glycophorin A that was used to increase the stability and specificity of this dimer by rational design of an inter-helical hydrogen bond. 

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