Insights into the structure and protein-protein interactions of the pro-apoptotic protein ASPP2.
ASPP (apoptosis-stimulating protein of p53) 2 is a pro-apoptotic protein that stimulates the p53-mediated apoptotic response. Here, we provide an overview of the structure and protein-protein interactions of ASPP2. The C-terminus of ASPP2 contains Ank (ankyrin) repeats and an SH3 domain (Src homology 3 domain). The Ank-SH3 domains mediate interactions between ASPP2 and numerous proteins involved in apoptosis such as p53 and Bcl-2. The proline-rich domain of ASPP2 is unfolded in its native state, but was not shown to mediate intermolecular interactions. Instead, it makes an intramolecular domain-domain interaction with the Ank-SH3 C-terminal domains of ASPP2. This intramolecular interaction between the unstructured proline-rich domain and the structured Ank-SH3 domains in ASPP2, which is possible due to the unfolded nature of the proline-rich domain, is proposed to have an important role in regulating the intermolecular interactions of ASPP2 with its partner proteins.
Rotem
S
S
Department of Organic Chemistry, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel.
Katz
C
C
Friedler
A
A
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011487:Protein Conformation
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C090468:TP53BP2 protein, human