Small angle X-ray scattering study of calreticulin reveals conformational plasticity

Organellar Calcium Buffers

“…The conformation of this region is highly dependent on variations in Ca 2þ concentrations within a physiological range (Corbett et al 2000). SAXS studies indicate that the Cdomain of calreticulin may be globular (Norgaard Toft et al 2008). Ca 2þ binding stabilizes the C-domain into a more compact, a-helical conformation; the Ca 2þ concentration required to induce this change, 400 mM, is well within the range of concentrations to which calreticulin would be exposed physiologically (Villamil Giraldo et al 2009).…”

“…The N-domain of calnexin, which is homologous to calreticulin, is primarily b-sheet and globular, with high homology to the structure of plant lectins, suggesting a role in the binding of monoglucosylated substrates to calreticulin as part of its chaperone role (Schrag et al 2001). Recent work using small angle X-ray scattering (SAXS) showed that the Ndomain of calreticulin itself is indeed globular and fits well onto modeled calnexin (Norgaard Toft et al 2008). The N-domain conformation is dynamic and is stabilized by oligosaccharide binding (Saito et al 1999;Conte et al 2007) and the binding of Ca 2þ at a high-affinity site (Corbett et al 2000;Conte et al 2007), though this binding does not affect its affinity for oligosaccharides (Conte et al 2007).…”

“…The P-domain adopts an extended conformation with antiparallel b-sheets between the repeated amino acid sequences; the domain as a whole protrudes out from the N-and C-domains (Ellgaard et al 2001a;Ellgaard et al 2001b). The extended protrusion requires a b-hairpin turn at amino acid residues 238 to 241; small angle X-ray scattering (SAXS) analyses indicate that this is in a spiral-like conformation (Norgaard Toft et al 2008). TROSY-NMR experiments showed that the tip of the P-domain protrusion accounts for the binding site of ERp57, an oxidoreductase-folding enzyme (Frickel et al 2002).…”

Immunological Activity Difference between Native Calreticulin Monomers and Oligomers

“…Mechanisms for CRT partial unfolding and possible oligomerization caused by chemical and physical (thermal) conditions have been studied in much detail [5], [18], [19], [35], [36]. Our BiFC experiments showed that intracellular CRT oligomerization could occur under 42°C at pH 6.5 (Fig.…”

Mutated calreticulin retains structurally disordered C terminus that cannot bind Ca2+: some mechanistic and therapeutic implications

“…A more ordered structure of the C terminus was reported based on modeling of small-angle X-ray scattering data but the effect of Ca 2+ concentration on this model is unclear. 10 …”