Structure of calcium prothrombin fragment 1 including the conformation of the Gla domain

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Abstract
The structure of Ca2+ prothrombin fragment 1 has been solved at 2.8-.ANG. resolution by X-ray crystallographic methods. Most of the Gla domain of fragment 1 (residues 1-48), which is highly homologous with the N-terminal regions of six other blood proteins, cannot be identified in the electron density map of the apo structure. This is not the case when crystals are grown in the presence of Ca2+ ions where the Gla domain exhibits as well-defined folded structure. The folding of the Gla domain is dominated by secondary structure: (a) 3.0 turns of .alpha.-helix (25%) and (b) five short .beta.-strands arranged into two .beta.-structural units (40%). The Cys18-Cys22 disulfide of the small conserved loop of Gla domains is close to a cluster of conserved aromatic residues. The resulting interaction is probably responsible for the fluorescence quenching event accompanying Ca2+ ion binding. Since the Gla domain approximately a discoid, all the Gla residues are easily accessible to solvent. The arrangement of the paired Gla residues (7-8, 20-21, 26-27) is highly suggestive in that they essentially line one edge of the Gla domain creating a potentially intense electronegative environment. This region might well be that associated with phospholipid binding. The kringle structure of Ca2+ fragment 1 is essentially indistinguishable from that of the apoprotein at this stage.