Crystal structure of the glutaredoxin-like protein SH3BGRL3 at 1.6 Angstrom resolution.
We report the 1.6 Angstrom resolution crystal structure of SH3BGRL3, a member of a new mammalian protein family of unknown function. The observed "thioredoxin fold" of SH3BGRL3 matches the tertiary structure of glutaredoxins, even in the N-terminal region where the sequence similarity between the two protein families is negligible. In particular, SH3BGRL3 displays structural modifications at the N-terminal Cys-x-x-Cys loop, responsible for glutathione binding and catalysis in glutaredoxins. The loop hosts a six residue insertion, yielding an extra N-terminal-capped helical turn, first observed here for the thioredoxin fold. This, together with deletion of both Cys residues, results in a substantial reshaping of the neighboring cleft, where glutathione is hosted in glutaredoxins. While not active in redox reaction and glutathione binding, SH3BGRL3 may act as an endogenous modulator of glutaredoxin activities by competing, with its fully conserved thioredoxin fold, for binding to yet unknown target proteins.
Nardini
Marco
M
Dipartimento di Fisica-INFM e Centro di Eccellenza per la Ricerca Biomedica, Università di Genova, Via Dodecaneso 33, 16146 Genoa, Italy.
Mazzocco
Michela
M
Massaro
Anna
A
Maffei
Massimo
M
Vergano
Alessandro
A
Donadini
Alessandra
A
Scartezzini
Paolo
P
Bolognesi
Martino
M
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000378:metabolism; D054477:Glutaredoxins; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010088:Oxidoreductases; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D055672:Static Electricity
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D054477:Glutaredoxins; D011506:Proteins; D011993:Recombinant Fusion Proteins; C487305:Sh3bgrl3 protein, mouse; D010088:Oxidoreductases