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ALL LIFE PROCESSES depend on the structures and interactions of
molecules in the living cells with macromolecules acting as information stores
and molecular machines. The latter is achieved mainly by proteins which
are ultimately self-assembling nanosolids. The current explosion in whole
genome sequencing is providing an unprecedented amount of
information on the blue prints (sequences) of
these protein machines. In order to understand "how it works" it
is necessary to have a starting model the three-dimensional structure
at atomic resolution.
Over the past year, the Protein Structure Group has determined the structures
of two proteins: PAI2 and PE 545. PAI2 controls tissue remodelling processes
in mammals. It does this by undergoing a dramatic structural change
which resembles the springing of a baited trap.
We now have high resolution structures of the "before" and "after" states.
In contrast, PE545 is a static, quantum mechanical machine. Its role is to
catch visible photons and transfer them to the photosynthetic reaction centre
protein which then uses the energy to establish an electrochemical gradient. PE
545 holds active chromophores in a specific geometric arrangement that ensures
high quantum yield for photon capture and transfer. This protein ensures
the survival of a marine algal cell that can live at low light levels. Our structure
is remarkable as it is at an unprecedented resolution for a 50kDa protein
we can see the hydrogen atoms! We are currently hunting the structure of
a human chloride ion channel protein NCC27 which would be the
first such structure. |
In order to solve structures, we need large amounts of high quality protein.
To ensure this, we are using all the tools of recombinant DNA technology.
Several projects are still at the cloning and expression stage, where we
are developing bacterial systems that will produce foreign proteins from
their genes. We are currently working on several proteins that assist other
proteins to adopt their correct three-dimensional structure. These are the
molecular chaperones that prevent a juvenile protein from illicit and
improper contacts with other proteins.
Finally, the aim is to understand the physical mechanisms behind
these processes. We are investigating the physical basis for fundamental asymmetries in proteins. This has led
to an examination of ß-structures at ultra high resolution. We have also
recently devised a novel enzyme mechanism for the rubisco the world's
most abundant enzyme. This mechanism is based on electrostatic transitions and
is likely to have general implications for a large class of enzymes.
Protein Structure Group
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