An evolutionary bridge to a new protein fold.
Arc repressor bearing the N11L substitution (Arc-N11L) is an evolutionary intermediate between the wild type protein, in which the region surrounding position 11 forms a beta-sheet, and a double mutant 'switch Arc', in which this region is helical. Here, Arc-N11L is shown to be able to adopt either the wild type or mutant conformations. Exchange between these structures occurs on the millisecond time scale in a dynamic equilibrium in which the relative populations of each fold depend on temperature, solvent conditions and ligand binding. The N11L mutation serves as an evolutionary bridge from the beta-sheet to the helical fold because in the mutant, Leu is an integral part of the hydrophobic core of the new structure but can also occupy a surface position in the wild type structure. Conversely, the polar Asn 11 side chain serves as a negative design element in wild type Arc because it cannot be incorporated into the core of the mutant fold.
Cordes
M H
MH
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Burton
R E
RE
Walsh
N P
NP
McKnight
C J
CJ
Sauer
R T
RT
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D002942:Circular Dichroism; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D019143:Evolution, Molecular; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009875:Operator Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012997:Solvents; D013050:Spectrometry, Fluorescence; D013696:Temperature; D013816:Thermodynamics; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins
D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D012997:Solvents; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins