title: The crystal structure of p13suc1, a p34cdc2-interacting cell cycle control protein.
abstract: p13suc1 binds to p34cdc2 kinase and is essential for cell cycle progression in eukaryotic cells. The crystal structure of S.pombe p13suc1 has been solved to 2.7 A resolution using data collected at the ESRF source, Grenoble, from both native crystals and crystals of a seleno-methionine derivative. The starting point for structure solution was the determination of the six selenium sites by direct methods. The structure is dominated by a four-stranded beta-sheet, with four further alpha-helical regions. p13suc1 crystallizes as a dimer in the asymmetric unit stabilized by the binding of two zinc ions. A third zinc site stabilizes the higher-order crystal packing. The sites are consistent with a requirement for zinc during crystal growth. A likely site for p13suc1-protein interaction is immediately evident on one face of the p13suc1 surface. This region comprises a group of conserved, exposed aromatic and hydrophobic residues below a flexible negatively charged loop. A conserved positively charged area would also present a notable surface feature in the monomer, but is buried at the dimer interface. p13suc1 is larger than its recently solved human homologue p9CKS2, with the extra polypeptide forming a helical N-terminal extension and a surface loop between alpha-helices 3 and 4. Notably, p13suc1 does not show the unusual beta-strand exchange that creates an intimate p9CKS2 dimer. p13suc1 cannot oligomerize to form a stable hexamer as has been proposed for p9CKS2.
authors.affiliation: Laboratory of Molecular Biophysics, Oxford, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Endicott
authors.forename: M E
authors.initials: ME
authors.lastname: Noble
authors.forename: E F
authors.initials: EF
authors.lastname: Garman
authors.forename: N
authors.initials: N
authors.lastname: Brown
authors.forename: B
authors.initials: B
authors.lastname: Rasmussen
authors.forename: P
authors.initials: P
authors.lastname: Nurse
authors.forename: L N
authors.initials: LN
authors.lastname: Johnson
mesh_terms: D000595:Amino Acid Sequence; D016203:CDC2 Protein Kinase / Q000378:metabolism; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins / Q000737:chemistry; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D017124:Conserved Sequence / Q000235:genetics; D003460:Crystallization; D018360:Crystallography, X-Ray; D005656:Fungal Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011494:Protein Kinases; D012568:Schizosaccharomyces / Q000737:chemistry; D029702:Schizosaccharomyces pombe Proteins; D015032:Zinc / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D029702:Schizosaccharomyces pombe Proteins; C051655:Suc1 protein, S pombe; D011494:Protein Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C083689:CKS2 protein, human; D015032:Zinc