How to untwist an alpha-helix: structural principles of an alpha-helical barrel.
Recent crystallographic studies have revealed that 12 alpha-helices can pack in an anti-parallel fashion to form a hollow cylinder of nearly uniform radius. In this architecture, which we refer to as an alpha-barrel, the helices are inclined with respect to the cylindrical axis, and thus they curve and twist. As with conventional coiled-coils, the helices of the barrel associate via "knobs-into-holes" interactions; however, their packing is distinct in several important ways. First, the alpha-barrel helices untwist in comparison with the helices found in two-stranded coiled-coils and, as a consequence of this distortion, their knobs approach closely one end of the complementary holes. This effect defines a requirement for particular size and shape of the protruding residues, and it is associated with a relative axial translation of the paired helices. Second, as each helix packs laterally with two neighbours, the helices have two sequence patterns that are phased to match the two interfaces. The two types of interface are not equivalent and, as one travels around the circumference of the cylinder's interior, they alternate between one type where the knobs approach the holes straight-on, and a second type in which they are inclined. The choice of amino acid depends on the interface type, with small hydrophobic side-chains preferred for the direct contacts and larger aliphatic side-chains for the inclined contacts. Third, small residues are found preferentially on the inside of the tube, in order to make the "wedge" angle between helices compatible with a 12-member tube. Finally, hydrogen-bonding interactions of side-chains within and between helices support the assembly. Using these salient structural features, we present a sequence template that is compatible with some underlying rules for the packing of helices in the barrel, and which may have application to the design of higher-order assemblies from peptides, such as nano-tubes. We discuss the general implications of relative axial translation in coiled-coils and, in particular, the potential role that this movement could play in allosteric mechanisms.
Calladine
C R
CR
Department of Engineering, University of Cambridge, Trumpington Street, Cambridge, CB2 1PZ, UK. crc@eng.cam.ac.uk
Sharff
A
A
Luisi
B
B
D000494:Allosteric Regulation; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry*; D001665:Binding Sites; D004926:Escherichia coli / Q000737:chemistry*; D029968:Escherichia coli Proteins; D006860:Hydrogen Bonding; D026901:Membrane Transport Proteins; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D055672:Static Electricity
D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; C073126:tolC protein, E coli