The alphabet of intrinsic disorder: II. Various roles of glutamic acid in ordered and intrinsically disordered proteins

Uversky, Vladimir N

leton-membrane linkage crucial for controlling cell shape changes. 189 since although the molecular mass of the phosphoprotein was shown to be about 44 kDa by sedimentation equilibrium analysis, it runs on 5-15% SDS-PAGE (SDS-PAGE) as a protein with a molecular mass of 75 kDa. 197 Later studies revealed that BSP is capable of nucleating the bone mineral hydroxyapatite and that this nucleation involves one or both of the glutamic acid-rich sequences suggesting that polycarboxylate sequences might represent a specific site for growth-modulating interactions between proteins and biological hydroxyapatite crystals. 198 Similarly, the ability of another acidic, non-collagenous protein of bone and dentin, osteonectin (also known as secreted protein, acidic, rich in cysteine), to bind to hydroxyapatite crystals is determined by its N-terminal region containing glutamic acid-rich sequences. 199 SPARC is a highly conserved acidic calcium-binding extracellular-matrix protein. 200 This matricellular glycoprotein is composed of three functional domains that are evolutionarily conserved in organisms ranging from nematodes to mammals. 201 Starting from the N-terminus, these functional domains are: a Ca 2+ -binding glutamic acid-rich acidic domain (domain I), a follistatin-like module (domain II), and an extracellular Ca 2+ -binding (EC) module that contains two EF-hands and two collagen-binding epitopes (domain III). Since domain I was not found in SPARC isolated from the starlet anemone Nematostella vectensis, it has been proposed that SPARC first evolved as a collagen-binding matricellular glycoprotein. 201 Human SPARC is a 303 residueslong protein that contains 34 glutamic acids, 15 of which are located within the N-terminal calcium binding region (residues 22-69). Although Xenopus laevis SPARC has a molecular mass of 32.6 kDa, based on SDS-PAGE analysis this protein has a molecular mass of 43 kDa. 200 NBP-45. In nuclei of mice cells, there is a nuclear protein NBP-45 related to the nuclear proteins HMG-14/-17. NBP-45 can function as a transcriptional activator, binds specifically to nucleosome core particles, 202 preferentially binds to euchromatin and modulates cellular transcription by counteracting linker histone-mediated chromatin compaction. 203 NBP-45 is composed of 406 amino acids and has several functional regions and domains: the N-terminal region (residues 1-85) contains three segments that are highly homologous to functionally important domains in the HMG-14/-17 protein family, namely a nuclear localization signal, a nucleosome binding domain and a chromatin unfolding domain, whereas the C-terminal region (residues 86-406) has 43.7% of negatively charged residues. 202 In fact, of the 110 glutamic acids and 44 aspartic acids found in NBP-45, 100 glutamic and 40 aspartic acids are located in this highly acidic region.