FIG. 1.

MsrB3 sequence. (A) Amino acid sequence alignments of the amino- and carboxy termini of representative mammalian MsrB3 orthologs (Homo sapiens, Oryctolagus cuniculus, Erinaceus europaeus, Felis catus, Bos taurus, Globicephala melas, Ceratothenium simum, Pteropus vampyrus, Ailuropoda melanoleuca, and Vombatus ursinus). Predicted signal sequences for ER targeting are highlighted in violet. Dashes indicate gaps in the alignment; dots indicate intervening sequence that is not shown. The CX₅C motif, including the identities of the residues between the two cysteines, is highly conserved. KDEL-like ER retention signals are present at the carboxy termini. (B) Sequence of the precursor of ER-localized human MsrB3 with secondary structure annotations according to the structure reported herein. The signal peptide is highlighted in violet/pink, with two arrows indicating possible cleavage sites generating the mature protein. The first arrow indicates the site predicted by using SignalP (37). The second site and resulting numbering of the mature sequence are according to UniProt (45). The KDEL-like ER retention signal (KAEL in human MsrB3) is highlighted in light blue. Cysteine amino acids are highlighted in yellow. The blue oval represents a zinc ion coordinated by cysteine residues. The active-site cysteine is indicated by an orange star, and the resolving cysteines are indicated by an overline labeled CX₅C. Cylinders indicate helices; arrows indicate β-strands. The dashed segment indicates a region for which no electron density was evident in the crystallographic maps. ER, endoplasmic reticulum; KAEL, Lys-Ala-Glu-Leu; KDEL, Lys-Asp-Glu-Leu; Msr, methionine sulfoxide reductase. Color images are available online.