A central component of the kallikrein-kinin system (KKS) is the cleavage of kininogen to generate short vasoactive peptides termed kinins and plasma kallikrein (KLKB) cleaves high molecular weight kininogen (HK) to generate principle vasoactive peptide bradykinin (BK). In addition to cleaving HK, PK is a central component of the contact system. Once activated, PK is capable of activating factor XII (FXII) and thereby amplifies the generation of FXIIa that reciprocally activates PK through a feedback system. Although PK and kininogen deficiency in humans does not manifest a clinical abnormality in bleeding, studies in mouse model systems of disease and have identified that PK and HK contribute to thrombus formation. Prekallikrien and homologous coagulation factor XI (FXI) are the only coagulation factors that circulate in plasma with a C-terminal protease domain and an N-terminal heavy chain of 4 repeats of the 90 residue apple domain. FXI and PK circulate in complex with co-factor HK; an interaction mediated through the D6 domain of HK with the apple domains of PK. The interaction of these two proteins is essential for PK substrate recruitment. We report the crystal structure of the heavy chain of prekallikrien revealing the 3D arrangement of the four apple domains. PK is monomeric compared to FXI which is a disulphide linked dimer and the structure describes the additional disulphide and changes in the A4 domain that contribute to this. We also describe novel ligand binding experiments and structure-function relationships of PK.