CRYSTALLOGRAPHIC STUDIES OF THE HUMAN PENTRAXINS, SERUM AMYLOID P COMPONENT AND C-REACTIVE PROTEIN. D. Thompson, I. J. Tickle, T. L. Blundell, M. B. Pepys1 & S. P. Wood2, Department of Crystallography, Birkbeck College, Malet Street, London, 1Immunological Medicine unit, Hammersmith Hospital, London, 2Department of Biochemistry, University of Southampton, Southampton
The crystal structure of the two major human pentraxins have been determined to medium resolution. The pentraxins are a protein family which exhibit five fold symmetry of subunits and are capable of calcium dependent binding. The two major human pentraxins are Human Serum Amyloid P Component (SAP), which is found bound to amyloid deposits in amyloidosis and Alzheimer's disease, and C-reactive protein (CRP), which is believed to have a role during the immune response. SAP and CRP share 52% sequence identity. SAP exists in the plasma as a decamer, two pentameric rings interacting face to face, each subunit consisting of 204 amino acids, whereas CRP exists as a single pentameric ring made up of subunits consisting of 206 amino acids.
Two CRP crystal forms have been grown. Both are tetragonal. One has a unit cell of a=b=275.81 and c=94.21, and contains 3 pentamers per asymmetric unit and the other is of unit cell a=b=190.31 and c=132.12, space group P43212, and contains two pentamers per asymmetric unit. A complete data set has been collected on this crystal form to a resolution of 3.0Å. Crystals have also been grown of decameric SAP. These are of spacegroup P21 and unit cell a=103.37 b=112.711 c=121.499 and [[beta]]=91.87 and contains 1 decamer per asymmetric unit. A complete data set has been collected on this crystal form to 2.5Å.
Both structures have been solved by molecular replacement using the pentameric structure of SAP (Emsley, J. et al. (1994) Nature vol. 367, p338-345) as a model.