Disordered Motifs and Domains in Cell Control
Poster Session I
8-POS Board 8
Investigating the Structural Basis for Recruitment of CBP/p300 by E2A
David N. Langelaan
, Alyssa K. Kirlin, Marina Lochead, Seth Chitayat, Steven P. Smith.
Queen's University, Kingston, Canada.
E2A is a transcription factor that is essential for proper regulation of B-lymphocyte development
and disruption of E2A through a t(1;19) chromosomal translocation is associated with acute
lymphoblastic leukemia. The product of the t(1;19) translocation is the oncoprotein E2A-PBX1
which contains the unstructured activation domains (AD) of E2A and most of the PBX1 protein,
including the DNA binding domain. Previous work from our group has determined that
leukemogenesis primarily requires AD1 of E2A and the KIX domain from CBP/p300. However,
the activation domains of E2A are able to recruit CBP/p300 in a cooperative manner, suggesting
that other modules of CBP/p300 may be involved in forming the E2A:CBP complex. The
objective of this study was to isolate other domains of CBP/300 which recognize E2A. Using
complementary biophysical techniques such as peptide microarrays, isothermal titration
calorimetry, pull-down experiments and nuclear magnetic resonance spectroscopy we have
determined that AD1 of E2A adopts a helical structure when it binds to the Taz2 domain of
CPB/p300. These results illustrate how the unstructured activation domains of E2A are able to
recognize multiple domains of CBP/p300, allowing for cooperative recruitment of CBP/p300 by
E2A.
9-POS Board 9
CD and NMR Conformational Preferences of Intrinsically Disordered Amphiphilic
Peptides: A New Class of Potential Targets in Drug Discovery
Diego Tesauro
1,2
, Marian Vincenzi
1
, Flavia A. Mercurio
2
, Antonella Accardo
1,2
, Luisa Ronga
3
,
Marilisa Leone
2
, Filomena Rossi
1,2
.
1
University of Naples "Federico II", Naples, Italy,
2
CNR, Naples, Italy,
3
University of Bordeaux,
Bordeaux, France.
Owing to the large panel of biological functions of peptides and their high specificity and
potency, the development of peptide-based therapeutic and diagnostic tools has received
increased interest. Peptide amphiphiles (PAs) are an emerging class of molecules in which a
bioactive peptide is covalently conjugate to a hydrophobic moiety1. Due to the coexistence in the
molecule of a hydrophilic peptide sequence and a hydrophobic group, PAs are able to self-
assemble spontaneously into a variety of nanostructures, such as monolayers, bilayers, and
vesicles. In this work we have synthesized predicted by MEDOR2 disordered peptide
sequences3 functionalized by alkyl chains, and connected by ethoxylic-based linker. The
structural properties in solution of these new PAs were investigated using CD, NMR and DLS.
The presence of the alkyl chains induces not only the self-assembly of these new PAs into
supramolecular aggregates but also a gain of structure within the disordered peptide. The design
of supramolecular systems, generated by joining a disordered peptide and a lipophilic moiety,
could drive the disordered peptide to fold into a stable structure. This structural modification
could be a promising route to develop a new class of bio-molecules for processes in which a
specific conformational rearrangement is required.
- 60 -
