Disordered Motifs and Domains in Cell Control
Monday Speaker Abstracts
Use of Host-like Peptide Motifs in Viral Proteins Is a Prevalent Strategy in Host-Virus
Interactions
M. Madan Babu
.
MRC Lab of Molecular Biology, Cambridge, United Kingdom.
Viruses interact extensively with host proteins, but the mechanisms controlling these interactions
are not well understood. We present a comprehensive analysis of eukaryotic linear motifs
(ELMs) in 2,208 viral genomes and reveal that viruses exploit molecular mimicry of host-like
ELMs to possibly assist in host-virus interactions. Using a statistical genomics approach, we
identify a large number of potentially functional ELMs and observe that the occurrence of ELMs
is often evolutionarily conserved but not uniform across virus families. Some viral proteins
contain multiple types of ELMs, in striking similarity to complex regulatory modules in host
proteins, suggesting that ELMs may act combinatorially to assist viral replication. Furthermore, a
simple evolutionary model suggests that the inherent structural simplicity of ELMs often enables
them to tolerate mutations and evolve quickly. Our findings suggest that ELMs may allow fast
rewiring of host-virus interactions, which likely assists rapid viral evolution and adaptation to
diverse environments.
Interaction Profiling Using Phage Peptidomes
Ylva Ivarsson
.
Uppsala University, Uppsala, Sweden.
Phage display is a powerful technique for specificity profiling of peptide-binding domains. Using
highly diverse combinatorial peptide phage libraries, the method is suited for the identification of
high affinity ligands with inhibitor potential. A complementary but considerably less explored
approach is the proteomic peptide phage display where expression products from exquisitely
designed oligonucleotide libraries are displayed on phage particles. Proteomic phage display can
be used to uncover protein-protein interactions of potential relevance for cell function. The
method is particularly suited for the discovery of interactions between peptide binding domains
and their target motifs
We recently generated phage libraries displaying all human C-terminal sequences using custom
oligonucleotide microarrays and used them to interrogate interactions of human protein-95/disks
large/zonula occludens-1 (PDZ) domains. We successfully identified novel PDZ domain
interactions of potential relevance to cellular signaling pathways and validated a subset of
interactions with a high success rate. I will present our recent results on how the combination of
combinatorial and proteomic peptide phage display can be used to elucidate preferences of
peptide binding domains and to identify targets of biological relevance.
Reference
Ivarsson, Y., Arnold, R., McLaughlin, M., Nim, S., Joshi, R., Ray, D., Liu, B., Teyra, J., Pawson,
T., Moffat, J., Li, S., Sidhu, S. S., & Sidhu, S. S. Large-scale interaction profiling of PDZ
domains through proteomic peptide-phage display using human and viral phage peptidomes.
(2014) Proc Natl Acad Sci U S A 111, 2542-2547.
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