Crystal structure of fragment D from human fibrinogen (click to enlarge)
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    NOTE: This description is quite
out of date. New posting will appear soon.

Our group is mainly concerned with the
structure and evolution of proteins. In this
regard, we have two quite distinct projects
under way. One is very general and has to
do with reconstructing the evolutionary
histories of a wide variety of proteins. This
is a computer-based study that draws upon
published sequence data for its raw material.
We employ a number of sequence searching
and alignment programs, many of which we
have written ourselves. Among the questions
we are trying to answer are: When did
prokaryotic organisms diverge from eukaryotes? How many rudimentary families of proteins are there? How are "new proteins" invented? All of these questions can be answered, given enough sequences to compare. 

    Our second major research interest is laboratory-based and deals with the invention and evolution of vertebrate blood plasma proteins, and expecially the clotting proteins. In the past, we have cloned and sequenced a number of these proteins from the most primitive of vertebrates, the lamprey. Comparison with the corresponding mammalian proteins has afforded us some important clues as to how these proteins function. We also succeeded in identifying equivalent gene products in even more distantly related creatures, including protochordates and invertebrates. Of all of these, we have focused most on the fibrinogen molecule. Our goal here is to understand how fibrin formation (clotting) occurs and was invented. In this regard, after many years of trying we managed to crystallize a native fibrinogen molecule (chicken fibrinogen = 320 KDa) and solved its X-ray structure. We have also solved the structure of various fibrinogen fragments with bound ligands involved in fibrin formation, and also factor XIII-generated crosslinked versions.

     The crystallography project should shed light not only on how clotting works but also on where some of the components came from. Fibrinogen is a multidomained mosaic protein, a key part of which is found in numerous other animal proteins, including various cytotactins (e.g., tenascin and T-cell factors).

















    

 
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Last Modified Sun. June 13, 2009