The ASPP interaction network: electrostatic differentiation between pro- and anti-apoptotic proteins

The ASPP proteins are apoptosis regulators: ASPP1 and ASPP2 promote, while iASPP inhibits, apoptosis. The mechanism by which these different outcomes are achieved is still unknown. The C‐terminal ankyrin repeats and SH3 domain (ANK‐SH3) mediate the interactions of the ASPP proteins with major apopto...

Full description

Saved in:
Bibliographic Details
Published in:Journal of molecular recognition 2011-03, Vol.24 (2), p.266-274
Main Authors: Benyamini, Hadar, Friedler, Assaf
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino Acids - metabolism
Ankyrin Repeat
Apoptosis
Apoptosis Regulatory Proteins - chemistry
Apoptosis Regulatory Proteins - metabolism
ASPP
ASPP2
Bcl-2
Binding
Binding Sites
Charging
computational studies
Electrostatics
iASPP
interaction network
Models, Molecular
Molecular Sequence Data
NF-kappa B - metabolism
NF-kappa-B
p53
Protein Binding
Protein Structure, Tertiary
Proteins
Proto-Oncogene Proteins c-bcl-2 - metabolism
Regulators
Residues
Sequence Alignment
Static Electricity
Surface Properties
Thermodynamics
Tumor Suppressor Protein p53 - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The ASPP proteins are apoptosis regulators: ASPP1 and ASPP2 promote, while iASPP inhibits, apoptosis. The mechanism by which these different outcomes are achieved is still unknown. The C‐terminal ankyrin repeats and SH3 domain (ANK‐SH3) mediate the interactions of the ASPP proteins with major apoptosis regulators such as p53, Bcl‐2, and NFκB. The structure of the complex between ASPP2ANK‐SH3 and the core domain of p53 (p53CD) was previously determined. We have recently characterized the individual interactions of ASPP2ANK‐SH3 with Bcl‐2 and NFκB, as well as a regulatory intramolecular interaction with the proline rich domain of ASPP2. Here we compared the ASPP interactions at two levels: ASPP2ANK‐SH3 with different proteins, and different ASPP family members with each protein partner. We found that the binding sites of ASPP2 to p53CD, Bcl‐2, and NFκB are different, yet lie on the same face of ASPP2ANK‐SH3. The intramolecular binding site to the proline rich domain overlaps the three intermolecular binding sites. To reveal the basis of functional diversity in the ASPP family, we compared their protein‐binding domains. A subset of surface‐exposed residues differentiates ASPP1 and ASPP2 from iASPP: ASPP1/2 are more negatively charged in specific residues that contact positively charged residues of p53CD, Bcl‐2, and NFκB. We also found a gain of positive charge at the non‐protein binding face of ASPP1/2, suggesting a role in electrostatic direction towards the negatively charged protein binding face. The electrostatic differences in binding interfaces between the ASPP proteins may be one of the causes for their different function. Copyright © 2010 John Wiley & Sons, Ltd.
ISSN:0952-3499
1099-1352
1099-1352
DOI:10.1002/jmr.1048