The relative positions of alanine residues in the hydrophobic core control the formation of two-stranded or four-stranded {alpha}-helical coiled-coils |
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Authors: | Monera Oscar D; Snnichsen Frank D; Hicks Les; Kay Cyril M; Hodges Robert S |
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Affiliation: | Department of Biochemistry and the Protein Engineering Network of Centres of Excellence, University of Alberta Edmonton, Alberta, Canada T6G 2H7 |
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Abstract: | The objective of this study was to investigate the positionaleffect of hydrophobic interactions in the -helical interfacein controlling the formation of two-stranded and four-strandedcoiled-coils. Two disulfide-bridged antiparallel coiled-coilswere designed which differ only in the position of a singleAla residue in the middle heptad: in peptide 2H the Ala residuesare in register (in the same rung), while in peptide 4H theyare not. Data from size-exclusion chromatography and sedimentationequilibrium experiments showed that under benign conditionspeptides 2H and 4H were two-stranded and four-stranded coiled-coilsrespectively. These results, in conjunction with molecular modelingstudies, suggest that when four Ala residues are in the sameplane of a potential four-stranded coiled-coil, the small sidechains of Ala would create a large cavity in the hydrophobicinterface of the potential four-stranded structure which isdestabilizing and favors the two-stranded, disulfide-bridgedcoiled-coil. In contrast, an alternating Leu-Ala hydrophobicpacking in the two planes distributes the potential cavity overa larger region, which may be partially filled by minor adjustmentsof the neighboring Leu side chains. As a result, there is stillsufficient hydrophobic contact to maintain the four-strandedstructure. |
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Keywords: | -helices/" target="_blank">gif" ALT="{alpha}" BORDER="0">-helices/ hydrophobic packing/ multiple helix coiled-coil/ protein folding |
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