Next Article in Journal / Special Issue
Coupled Folding and Specific Binding: Fishing for Amphiphilicity
Previous Article in Journal
Comparison of Free Energy Surfaces Calculations from Ab Initio Molecular Dynamic Simulations at the Example of Two Transition Metal Catalyzed Reactions
Previous Article in Special Issue
Accounting for Large Amplitude Protein Deformation during in Silico Macromolecular Docking
Int. J. Mol. Sci. 2011, 12(2), 1410-1430; doi:10.3390/ijms12021410
Article

Anchoring Intrinsically Disordered Proteins to Multiple Targets: Lessons from N-Terminus of the p53 Protein

1,2,3 and 1,2,3,*
1 State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China 2 Center for Theoretical Biology, Peking University, Beijing 100871, China 3 Beijing National Laboratory for Molecular Sciences, Peking University, Beijing 100871, China
* Author to whom correspondence should be addressed.
Received: 25 January 2011 / Revised: 10 February 2011 / Accepted: 16 February 2011 / Published: 23 February 2011
(This article belongs to the Special Issue Advances in Molecular Recognition)
View Full-Text   |   Download PDF [1580 KB, uploaded 19 June 2014]   |   Browse Figures

Abstract

Anchor residues, which are deeply buried upon binding, play an important role in protein–protein interactions by providing recognition specificity and facilitating the binding kinetics. Up to now, studies on anchor residues have been focused mainly on ordered proteins. In this study, we investigated anchor residues in intrinsically disordered proteins (IDPs) which are flexible in the free state. We identified the anchor residues of the N-terminus of the p53 protein (Glu17–Asn29, abbreviated as p53N) which are involved in binding with two different targets (MDM2 and Taz2), and analyzed their side chain conformations in the unbound states. The anchor residues in the unbound p53N were found to frequently sample conformations similar to those observed in the bound complexes (i.e., Phe19, Trp23, and Leu26 in the p53N-MDM2 complex, and Leu22 in the p53N-Taz2 complex). We argue that the bound-like conformations of the anchor residues in the unbound state are important for controlling the specific interactions between IDPs and their targets. Further, we propose a mechanism to account for the binding promiscuity of IDPs in terms of anchor residues and molecular recognition features (MoRFs).
Keywords: anchor residue; intrinsically disordered proteins; binding promiscuity; molecular recognition features; p53; MDM2; Taz2 anchor residue; intrinsically disordered proteins; binding promiscuity; molecular recognition features; p53; MDM2; Taz2
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share & Cite This Article

Export to BibTeX |
EndNote


MDPI and ACS Style

Huang, Y.; Liu, Z. Anchoring Intrinsically Disordered Proteins to Multiple Targets: Lessons from N-Terminus of the p53 Protein. Int. J. Mol. Sci. 2011, 12, 1410-1430.

View more citation formats

Supplements

Related Articles

Article Metrics

Comments

Citing Articles

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert