Abstract
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 β-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 β-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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1129-1132 |
| Number of pages | 4 |
| Journal | Nature Structural Biology |
| Volume | 7 |
| Issue number | 12 |
| DOIs | |
| State | Published - 2000 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Biochemistry
- Structural Biology
- Genetics
Cite this
An evolutionary bridge to a new protein fold. / Cordes, Matthew Hj; Burton, Randall E.; Walsh, Nathan P.; McKnight, C. James; Sauer, Robert T.
In: Nature Structural Biology, Vol. 7, No. 12, 2000, p. 1129-1132.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - An evolutionary bridge to a new protein fold
AU - Cordes, Matthew Hj
AU - Burton, Randall E.
AU - Walsh, Nathan P.
AU - McKnight, C. James
AU - Sauer, Robert T.
PY - 2000
Y1 - 2000
N2 - 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 β-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 β-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.
AB - 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 β-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 β-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.
UR - http://www.scopus.com/inward/record.url?scp=0033668488&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033668488&partnerID=8YFLogxK
U2 - 10.1038/81985
DO - 10.1038/81985
M3 - Article
C2 - 11101895
AN - SCOPUS:0033668488
VL - 7
SP - 1129
EP - 1132
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
SN - 1545-9993
IS - 12
ER -