STRUCTURE OF HUMAN PLASMINOGEN KRINGLE-4 AT 1.68 ANGSTROM AND 277 K -A POSSIBLE STRUCTURAL ROLE OF DISORDERED RESIDUES

Despite considerable effort to elucidate the functional role of the kr ingle domains, relatively little is known about interactions with othe r protein domains. Most of the crystal structures describe the interac tions at the kringle active site. This study suggests a novel way to i nterpret structural results such as disorder located away from an acti ve site. The crystal structure of human plasminogen kringle 4 (PGK4) h as been refined against 10-1.68 Angstrom resolution X-ray data (R-merg e = 3.7%) to the standard crystallographic R=14.7% using the program X -PLOR. The crystals of PGK4 showed significant instability in cell dim ensions (changes more than 1.5 Angstrom) even at 277 K. The refinement revealed structural details not observed before [Mulichak, Tulinsky & Ravichandran (1991). Biochemistry, 30, 10576-10588], such as clear de nsity for additional side chains and more extensive disorder. Discrete disorder was detected for residues S73, S78, T80, S89, S91, S92, M112 , S132, C138 and K142. Most of the disordered residues form two patche s on the surface of the protein. This localized disorder suggests that these residues may play a role in quaternary interactions and possibl y form an interface with the other domains of proteins that contain kr ingles, such as plasminogen. Although, an additional residue D65 was r efined at the beginning of the sequence, still more residues near the peptide cleavage site must be disordered in the crystal.