Title : Calcium binding
domains and calcium-induced conformational transition of
SPARC /
BM-40 /
osteonectin , an extracellular
glycoprotein expressed in mineralized and nonmineralized tissues
Abstract :
- SPARC , BM-40 , and osteonectin are identical or very closely related extracellular proteins of apparent Mr 43,000 (Mr 33,000 predicted from sequence)
- They were originally isolated from parietal endoderm cells, basement membrane producing tumors, and bone, respectively, but are rather widely distributed in various tissues
- In view of the calcium binding activity reported for osteonectin , we analyzed the SPARC sequence and found two putative calcium binding domains
- One is an N-terminal acidic region with clusters of glutamic acid residues
- This region, although neither gamma-carboxylated nor homologous, resembles the gamma-carboxyglutamic acid ( Gla ) domain of vitamin K dependent proteins of the blood clotting system in charge density, size of negatively charged clusters, and linkage to the rest of the molecule by a cysteine-rich domain
- The other region is an EF-hand calcium binding domain located near the C-terminus
- A disulfide bond between the E and F helix is predicted from modeling the EF-hand structure with the known coordinates of intestinal calcium binding protein
- The disulfide bridge apparently serves to stabilize the isolated calcium loop in the extracellular protein
- As observed for cytoplasmic EF-hand-containing proteins and for Gla domain containing proteins , a major conformational transition is induced in BM-40 upon binding of several Ca2 + ions
- This is accompanied by a 35% increase in alpha-helicity
- A pronounced sigmoidicity of the dependence of the circular dichroism signal at 220 nm on calcium concentration indicates that the process is cooperative
- In view of its properties, abundance, and wide distribution, it is proposed that SPARC / BM-40 / osteonectin has a rather general regulatory function in calcium-dependent processes of the extracellular matrix
Output (sent_index, trigger,
protein,
sugar,
site):
- 0. glycoprotein, , BM-40, -, -
- 0. glycoprotein, , glycoprotein, -, -
Output(Part-Of) (sent_index,
protein,
site):
- 0. BM-40, domains
- 3. SPARC, sequence
- 5. Gla, domain
- 5. proteins, domain
- 9. Gla, domain
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):