Abstract
Cyclin-dependent kinase (Cdk) inhibitor p21Waf1/Cip1/Sdi1 a multifunctional protein, has a major role as tumor suppressor, mediating G1/S arrest through inhibition of Cdks. Recent biological studies of Cyclin D1/Cdk4 have proposed that p21 C-terminal domain (p21CT) plays a key role as a potent Cdk4 inhibitor. We report here solution structures of p21CT for both the free and Cdk4-bound forms using 2D transferred NOE spectroscopy and dynamical simulated annealing calculations. Even though p21CT peptide is very flexible in the free state, when it bound to Cdk4, the structure becomes well structured in the binding domain. Therefore we propose that p21CT experiences an extensive conformational change upon Cdk4 binding. This structural change of p21CT may suggest the molecular mechanism of p21 for specificity and inhibition mode to assemble different cyclin-Cdk complexes. Especially, our data suggests that the D149FYHSKRR156 region of p21 is critical for Cdk4 binding, indicating that the major driving force for complex originates from hydrophobic interaction between p21 and Cdk4.
| Original language | English |
|---|---|
| Pages (from-to) | 419-427 |
| Number of pages | 9 |
| Journal | Journal of Biomolecular Structure and Dynamics |
| Volume | 19 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2001 Jan 1 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Structural Biology
- Molecular Biology
Cite this
}
Solution structure of p21Waf1/Cip1/Sdi1 C-terminal domain bound to Cdk4. / Sung, Yoon Hui; Shin, Joon; Shin, Junghyu; Lee, Weon Tae.
In: Journal of Biomolecular Structure and Dynamics, Vol. 19, No. 3, 01.01.2001, p. 419-427.Research output: Contribution to journal › Article
TY - JOUR
T1 - Solution structure of p21Waf1/Cip1/Sdi1 C-terminal domain bound to Cdk4
AU - Sung, Yoon Hui
AU - Shin, Joon
AU - Shin, Junghyu
AU - Lee, Weon Tae
PY - 2001/1/1
Y1 - 2001/1/1
N2 - Cyclin-dependent kinase (Cdk) inhibitor p21Waf1/Cip1/Sdi1 a multifunctional protein, has a major role as tumor suppressor, mediating G1/S arrest through inhibition of Cdks. Recent biological studies of Cyclin D1/Cdk4 have proposed that p21 C-terminal domain (p21CT) plays a key role as a potent Cdk4 inhibitor. We report here solution structures of p21CT for both the free and Cdk4-bound forms using 2D transferred NOE spectroscopy and dynamical simulated annealing calculations. Even though p21CT peptide is very flexible in the free state, when it bound to Cdk4, the structure becomes well structured in the binding domain. Therefore we propose that p21CT experiences an extensive conformational change upon Cdk4 binding. This structural change of p21CT may suggest the molecular mechanism of p21 for specificity and inhibition mode to assemble different cyclin-Cdk complexes. Especially, our data suggests that the D149FYHSKRR156 region of p21 is critical for Cdk4 binding, indicating that the major driving force for complex originates from hydrophobic interaction between p21 and Cdk4.
AB - Cyclin-dependent kinase (Cdk) inhibitor p21Waf1/Cip1/Sdi1 a multifunctional protein, has a major role as tumor suppressor, mediating G1/S arrest through inhibition of Cdks. Recent biological studies of Cyclin D1/Cdk4 have proposed that p21 C-terminal domain (p21CT) plays a key role as a potent Cdk4 inhibitor. We report here solution structures of p21CT for both the free and Cdk4-bound forms using 2D transferred NOE spectroscopy and dynamical simulated annealing calculations. Even though p21CT peptide is very flexible in the free state, when it bound to Cdk4, the structure becomes well structured in the binding domain. Therefore we propose that p21CT experiences an extensive conformational change upon Cdk4 binding. This structural change of p21CT may suggest the molecular mechanism of p21 for specificity and inhibition mode to assemble different cyclin-Cdk complexes. Especially, our data suggests that the D149FYHSKRR156 region of p21 is critical for Cdk4 binding, indicating that the major driving force for complex originates from hydrophobic interaction between p21 and Cdk4.
UR - http://www.scopus.com/inward/record.url?scp=0035699891&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035699891&partnerID=8YFLogxK
U2 - 10.1080/07391102.2001.10506751
DO - 10.1080/07391102.2001.10506751
M3 - Article
C2 - 11790141
AN - SCOPUS:0035699891
VL - 19
SP - 419
EP - 427
JO - Journal of Biomolecular Structure and Dynamics
JF - Journal of Biomolecular Structure and Dynamics
SN - 0739-1102
IS - 3
ER -