Significance of Knotted Structures for Function of Proteins and Nucleic Acids
Thursday Abstracts
Folding of Nascent Chains of Knotted Proteins
Nicole Lim, Anna Mallam, Elin Sivertsson, Joe Rogers, Danny Hsu, Laura Itzhaki,
Sophie
Jackson
.
University of Cambridge, Cambridge, United Kingdom.
Since 2000, when they were first identified by Willie Taylor, the number of knotted proteins
within the pdb has increased and there are now nearly 300 such structures. The polypeptide chain
of these proteins forms a topologically knotted structure. There are now examples of proteins
which form simple 31 trefoil knots, 41, 52 Gordian knots and 61 Stevedore knots. Knotted
proteins represent a significant challenge to both the experimental and computational protein
folding communities. When and how the polypeptide chain knots during the folding of the
protein poses an additional complexity to the folding landscape.
We have been studying the structure, folding and function of two types of knotted proteins – the
31-trefoil knotted methyltransferases and 52-knotted ubiquitin C-terminal hydrolases. The talk
will focus on our folding studies on knotted trefoil methyltransferases and will include our recent
work using cell free in vitro translation systems to probe the folding of nascent chains of knotted
proteins. This approach has also been used to show that GroEL/GroES play a role in the folding
of these proteins in vivo. New results on the degradation of knotted proteins by the bacterial
ClpXClpP system will be presented.
Exploring the Coordinated Functional and Folding Landscapes of Knotted Proteins
Patricia Jennings
.
UCSD, La Jolla, USA.
Flexibility and conformational changes allow proteins to perform the biological processes, such
as ligand binding, oligomerization, conformational rearrangements and catalysis. Modulation of
the dynamic states within the folded ensemble of a protein connect folded (or unfolded) states
with biological functional states. Therefore, the interplay between a protein’s structure, fold, and
function add complexity to the already delicate heterogeneous energy balance between
functional states. Clusters of frustrated interactions within various conformational states are
beginning to be identified as regions within protein scaffolds that may correlate with functional
regions. In our work we explore the hypothesis that regions with competing geometric restraints
that result in frustrated regions on the energy landscape of a given protein have both folding and
functional relevance. Of the structurally unique, yet significant knotted conformations available
in nature, the SPOUT and cysteine knot classes, both demonstrate these coordinated, yet
complex interactions and are the subject of our current explorations.
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