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Volume 10, Issue 8 (Suppl) J Proteomics Bioinform, an open access journal
ISSN: 0974-276X Structural Biology 2017
September 18-20, 2017
9th International Conference on
Structural Biology
September 18-20, 2017 Zurich, Switzerland
On the importance of intrinsically disordered segments in multidomain proteins: The example of the
interplay between STAM2, AMSH and polyubiquitin chains
Olivier Walker, Maggy Hologne, Minh-ha Nguyen, Marie Martin and Henry Kim
Institute of Science Analytiques, France
S ince more than three decades, structural biology has provided an impressive number of structures of folded proteins that
allowed the understanding of their function. Recent studies on intrinsically disordered proteins (IDP) or intrinsically
disordered segments (IDS) containing proteins have revealed that a specific fold is not necessary to establish a given interaction.
Furthermore, multidomain proteins can simultaneously present well folded domains and highly flexible linkers that bestow
a high flexibility to the entire protein. Such a flexibility allows to adopt a given structural organization and induce further
interactions with possible multiple partners. Such IDS are now recognized as key players in the cell machinery, notably as
mediator or modulator of protein-protein interactions or as signaling hub. As an example, we focus on the three domains
construct VUS (VHS-UIM-SH3) of the STAM2 protein that harbors two flexible linkers of 20 amino acids. By means of NMR
spin relaxation and SAXS, we show that these regions are highly flexible and that the complete protein could be described by an
ensemble of conformations rather than a unique structure. The result is an exquisite propensity to interact with polyubiquitin
chains through each of STAM2's domains. Indeed, Lys63 di-ubiquitin is binding to the VHS, UIM and SH3 domains of STAM2
with roughly the same affinity. At the same time, AMSH, a deubiquitinating enzyme is free to interact with the SH3 domain
of STAM2 and outcompetes Lys-63 di-ubiquitin chains. It encourages us to propose a model where a specific structural
organization between three different proteins allows the specific cleavage of polyubiquitin chains. This is rendered possible
only by the high flexibility of the IDS of STAM2.
Biography
Olivier Walker has a strong expertise in NMR methodology and computational methods. More specifically, he has developed original approaches aiming at the
determination of the structure and dynamics of polyubiquitin chains. Altogether, he can tackle some important questions raised in the field of life science by means of
NMR, SAXS, SANS and computational approaches. He has also developed different programs related to the analysis of NMR spin relaxation and the determination
of the relative orientation of different domains in multidomain proteins. More recently he has focused on different approaches aiming at the incorporation of NMR
data into molecular dynamics simulations.
Olivier Walker et al., J Proteomics Bioinform 2017, 10:8(Suppl)
DOI: 10.4172/0974-276X-C1-0101