Research Summary
The research interests of the Rees group emphasize the general area
of structural bioenergetics, using crystallographic and functional approaches
to characterize water-soluble and membrane proteins participating in
various energy transduction pathways. Studies of metalloproteins
containing complex cofactors with either molybdenum or tungsten have
defined the unusual structures of the FeMo-cofactor of nitrogenase
and the more widespread Mo-cofactor that participate in basic reactions
of the biological nitrogen and sulfur cycles. Studies of integral
membrane proteins have emphasized energy transduction processes associated
with photosynthetic and respiratory processes, mechanosensation,
and of ABC transporter systems that mediate nutrient uptake into
bacteria.
Metalloproteins Our work on metalloproteins
has centered on proteins that incorporate unusual molybdenum and
tungsten containing centers, including the FeMo-cofactor of nitrogenase
and the more widespread molybdenum cofactor that participate in many
of the basic reactions of the biological nitrogen and sulfur cycles.
We have determined structures for the nitrogenase FeMo-cofactor and
the pterin containing molybdenum-cofactor, which defined the structural
biology of molybdenum and tungsten, the only second and third row
transition metals to be utilized biologically. From a structural
bioenergetics perspective, nitrogenase is also of interest as a structurally
characterized energy transduction system that couples nucleotide
hydrolysis to redox chemistry, and exhibits striking parallels to
nucleotide-dependent signal transduction systems.
Membrane Proteins We are particularly interested
in transporters and channels that exist in multiple conformational
states that are sensitive to the binding of ligands, changes in membrane
potential or the application of mechanical forces. Our long-term goal
is to structurally define selected transporters and channels in distinct
functional states to understand how the conformations of membrane proteins
are coupled to the cellular environment. Systems of current interest
include ATP Binding Cassette (ABC) transporters that utilize the binding
and hydrolysis of ATP to translocate ligands across the membrane, and
prokaryotic mechanosensitive channels (Msc), including those of large
(MscL) and small (MscS) conductance that couple channel gating with
membrane tension. We are also interested in exploring the general parallels
between ABC transporters and nitrogenase in terms of the coupling between
nucleotide state and the formation of distinct complexes that are crucial
for mediating unidirectional translocation of ligands (nutrients and
electrons, respectively). In addition to their functional implications,
structural studies of membrane proteins are of general interest to
address the consequences of folding in a predominantly nonaqueous environment.
