Properties of the SPP1 auxiliary protein gp12.
A, Gp12 amino acid sequence showing position of the tag fused to its amino terminus. GXY triplets are underlined. The intermolecular collagen-like triple helix and α-helix predicted by bioinformatics are shown above the sequence. The collagenase cut of tag-gp12 inside the collagen-like sequence motif and peptides obtained from mass spectrometry analysis (E and F) are shown below. B, RH determination of native and unfolded-refolded tag-gp12. Native (dotted line) and tag-gp12 heated for 5 min at 90 °C and transferred directly to ice (continuous line) were analyzed by SEC at 16 °C as described under “Experimental Procedures.” The elution positions of thyroglobulin (RH = 85 Å), γ-globulin (RH = 48 Å), ovalbumin (RH = 30,5 Å), and myoglobin (RH = 20,7 Å) used to calibrate the column are indicated by arrows. Kav (partition coefficient) was calculated as described (35). mAU, milli absorbance units. C, sedimentation velocity of tag-gp12 at 220,000 × g (loading concentration of 1 mg/ml, 16 °C run). Gp12 has a sedimentation coefficient of 1.7 S (s20,w = 2.2 S). D, sedimentation equilibrium of tag-gp12 at 16,300 × g (loading concentration of 0.8 mg/ml, 16 °C run). The data (dots) were fit using a trimer model (continuous line). The best fit was obtained for a single species with an average mass of 31,270 ± 590 Da. The top panels in C and D show the deviation of experimental points from fitted curves. E and F, cleavage of tag-gp12 with collagenase VII analyzed by SDS-PAGE (inset in E) and mass spectrometry. The observed ion mass (4406.15 Da) in MALDI-TOF (E) is attributed to peptide 20–64 of the gp12 sequence, identifying the proteolysis site shown in A. The same peptide was detected by LC-MS/MS spectrometry, which also showed the presence of three other peptides, resulting from collagenase cleavage at the same position (F). The LS-MS/MS analysis had a tag-gp12 sequence coverage of 89%. For clarity, only the peptides in which one end was generated by the collagenase cleavage are listed in F. Those peptides were absent in the analysis of tag-gp12 not treated with collagenase.