Properties of the thioredoxin fold superfamily are modulated by a single amino acid residue.
The ubiquitous thioredoxin fold proteins catalyze oxidation, reduction, or disulfide exchange reactions depending on their redox properties. They also play vital roles in protein folding, redox control, and disease. Here, we have shown that a single residue strongly modifies both the redox properties of thioredoxin fold proteins and their ability to interact with substrates. This residue is adjacent in three-dimensional space to the characteristic CXXC active site motif of thioredoxin fold proteins but distant in sequence. This residue is just N-terminal to the conservative cis-proline. It is isoleucine 75 in the case of thioredoxin. Our findings support the conclusion that a very small percentage of the amino acid residues of thioredoxin-related proteins are capable of dictating the functions of these proteins.
Ren
Guoping
G
Howard Hughes Medical Institute, Departments of Molecular, Cellular, and Developmental Biology and Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
Stephan
Daniel
D
Xu
Zhaohui
Z
Zheng
Ying
Y
Tang
Danming
D
Harrison
Rosemary S
RS
Kurz
Mareike
M
Jarrott
Russell
R
Shouldice
Stephen R
SR
Hiniker
Annie
A
Martin
Jennifer L
JL
Heras
Begoña
B
Bardwell
James C A
JC
D000595:Amino Acid Sequence; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007532:Isoleucine / Q000737:chemistry; D007700:Kinetics; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry; D011392:Proline / Q000737:chemistry; D011487:Protein Conformation; D019704:Protein Disulfide-Isomerases / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013879:Thioredoxins / Q000737:chemistry*
D029968:Escherichia coli Proteins; D007532:Isoleucine; D013879:Thioredoxins; D011392:Proline; D010088:Oxidoreductases; D019704:Protein Disulfide-Isomerases; C526648:dsbA protein, E coli