 |
PDBsum entry 2jgz
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Cyclin b and cyclin a confer different substrate recognition properties on cdk2.
|
|
|
Authors
|
|
N.R.Brown,
E.D.Lowe,
E.Petri,
V.Skamnaki,
R.Antrobus,
L.N.Johnson.
|
|
|
Ref.
|
|
Cell Cycle, 2007,
6,
1350-1359.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The transitions of the cell cycle are regulated by the cyclin dependent protein
kinases (CDKs). The cyclins activate their respective CDKs and confer substrate
recognition properties. We report the structure of phospho-CDK2/cyclin B and
show that cyclin B confers M phase-like properties on CDK2, the kinase that is
usually associated with S phase. Cyclin B produces an almost identical activated
conformation of CDK2 as that produced by cyclin A. There are differences between
cyclin A and cyclin B at the recruitment site, which in cyclin A is used to
recruit substrates containing an RXL motif. Because of sequence differences this
site in cyclin B binds RXL motifs more weakly than in cyclin A. Despite
similarity in kinase structures, phospho-CDK2/cyclin B phosphorylates
substrates, such as nuclear lamin and a model peptide derived from p107, at
sequences SPXX that differ from the canonical CDK2/cyclin A substrate
recognition motif, SPXK. CDK2/cyclin B phosphorylation at these non-canonical
sites is not dependent on the presence of a RXL recruitment motif. The p107
peptide contains two SP motifs each followed by a non-canonical sequence of
which only one site (Ser640) is phosphorylated by pCDK2/cyclin A while two sites
are phosphorylated by pCDK2/cyclin B. The second site is too close to the RXL
motif to allow the cyclin A recruitment site to be effective, as previous work
has shown that there must be at least 16 residues between the catalytic site
serine and the RXL motif. Thus the cyclins A and B in addition to their role in
promoting the activatory conformational switch in CDK2, also provide
differential substrate specificity.
|
|
|
|
|
|
|
