Small angle X-ray scattering study of calreticulin reveals conformational plasticity.
Calreticulin plays a central role in vital cell processes such as protein folding, Ca(2+) homeostasis and immunogenicity. Even so, only limited three-dimensional structural information is presently available. We present a series of Small-Angle X-ray Scattering data on human placenta calreticulin. The data from the calreticulin monomer reveal the shape of calreticulin in solution: The previously structurally un-described C-terminal is seen as a globular domain, and the P-domain beta-hairpin extends from the N-domain in a spiral like conformation. In the calreticulin solution dimer, the N-, C-, and P-domains are easily identified, and the P-domain is in an extended conformation connecting to the second calreticulin molecule. The SAXS solution data enables the construction of a medium-resolution model of calreticulin. In the light of the unresolved chaperone mechanism of calreticulin and calnexin, we discuss the functional consequences of the conformational plasticity of the calreticulin P-domain.
Department of Medicinal Chemistry, University of Copenhagen, DK-2100 Copenhagen, Denmark. knt@farma.ku.dk
Katrine
K
Nørgaard Toft
Nanna
N
Larsen
Flemming
F
Steen Jørgensen
Peter
P
Højrup
Gunnar
G
Houen
Bente
B
Vestergaard
D037282:Calreticulin / Q000737:chemistry*; D019281:Dimerization; D005260:Female; D006801:Humans; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry; D010920:Placenta / Q000737:chemistry; D011247:Pregnancy; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D053838:Scattering, Small Angle; D012996:Solutions; D014961:X-Ray Diffraction
D037282:Calreticulin; D010446:Peptide Fragments; D012996:Solutions