A novel structure of an antikinase and its inhibitor.
In Bacillus subtilis, the KipI protein is a regulator of the phosphorelay governing the onset of sporulation. KipI binds the relevant sensor histidine kinase, KinA, and inhibits the autophosphorylation reaction. Gene homologues of kipI are found almost ubiquitously throughout the bacterial kingdom and are usually located adjacent to, and often fused with, kipA gene homologues. In B. subtilis, the KipA protein inhibits the antikinase activity of KipI thereby permitting sporulation. We have used a combination of biophysical techniques in order to understand the domain structure and shape of the KipI-KipA complex and probe the nature of the interaction. We also have solved the crystal structure of TTHA0988, a Thermus thermophilus protein of unknown function that is homologous to a KipI-KipA fusion. This structure, which is the first to be described for this class of proteins, provides unique insight into the nature of the KipI-KipA complex. The structure confirms that KipI and KipA are proteins with two domains, and the C-terminal domains belong to the cyclophilin family. These cyclophilin domains are positioned in the complex such that their conserved surfaces face each other to form a large "bicyclophilin" cleft. We discuss the sequence conservation and possible roles across species of this near-ubiquitous protein family, which is poorly understood in terms of function.
School of Molecular Bioscience, University of Sydney, NSW 2006, Australia.
David A
DA
Jacques
David B
DB
Langley
Robert M G
RM
Hynson
Andrew E
AE
Whitten
Ann
A
Kwan
J Mitchell
JM
Guss
Jill
J
Trewhella
D001412:Bacillus subtilis / Q000201:enzymology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D000071677:Histidine Kinase; D008958:Models, Molecular; D011485:Protein Binding; D025941:Protein Interaction Mapping; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism*; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D016963:Thermus thermophilus / Q000201:enzymology*
D001426:Bacterial Proteins; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D000071677:Histidine Kinase