Significance of Knotted Structures for Function of Proteins and Nucleic Acids
Poster Session II
29 – POS Board 1
Unbinding and Unfolding of Adhesion Protein Complexes in Stretching Simulations
Bartosz Rózycki
1
,
Lukasz Mioduszewski
2
, Marek Cieplak
1
.
2
University of Warsaw, Warsaw, Poland.
1
Polish Academy of Sciences, Warsaw, Poland,
We made coarse-grained simulations to analyze mechanically induced dissociation and unfolding
of the protein complex CD48-2B4. This heterodimer is an indispensable component of the
immunological system: 2B4 is a receptor on natural killer cells whereas CD48 is expressed on
surfaces of various immune cells.
We find that the dissociation process strongly depends on the direction of pulling and may
follow different pathways. When pulling with a constant speed, there are several force peaks
before the subunits disconnect. In some pathways the final peak (from tensile forces involved in
the act of separation) is lower than an earlier peak, associated with shear-involving unraveling of
individual subunits (mainly CD48). These results suggest that measuring the highest force in
AFM pulling experiments may not provide direct information about adhesion forces.
In living cells both subunits are anchored in cell membranes by their C-terminal domains.
Interestingly, pulling by the C-termini results in the simplest scenario, with only one force peak
and no different pathways. On the contrary, pulling by the N-terminus of the CD48 subunit
always results in two pathways, no matter which other terminus is being pulled.
In constant force simulations, dissociation process changes if the pulling force exceeds the
maximum force from constant speed simulations. Dependence of unfolding time on force is
different in these two force regimes.
In both constant speed and force simulations, the CD48-2B4 interface can be divided into three
distinct patches that act as separate units when resisting the pulling forces. They may break
simultaneously or separately, depending on the pathway and pulling direction.
The simulation procedure was verified by simulating Synaptotagmin 1, a membrane-trafficking
multidomain protein, which was also studied experimentally. Our simulation results agree with
experimental findings.
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