Professor, Molecular Biology and Biochemistry
School of Biological Sciences

Protein structure, function, post-translational modification; fibrinogen

The elucidation of the covalent structure of a protein is a prerequisite for the understanding of its biological function. In our group, the primary structures, post-translational modifications, and structure-function relationships of several biologically and medically important proteins are being studied. Fibrinogen is a central protein of blood coagulation and has a molecular weight of about 340 kDa. The proteolytic enzyme thrombin converts it into an insoluble form, the fibrin clot. The diseases related to the blood coagulation system are of great medical interest, and therefore it is important to understand the structure-function relationships in fibrinogen. Genetically determined, dysfunctional variants of fibrinogen can be used as highly specific probes for these relationships, as each mutation which causes an amino acid substitution may provide clues about a functional site.

So far, the variants from over 60 families have been structurally elucidated, many of them by our research group. However, in every person fibrinogen is also extensively post-translationally modified , and the identification and functional properties of the corresponding variants are also being studied in the laboratory. The investigations are relevant for the understanding of the role of fibrinogen in thrombotic cardiovascular disease and bleeding disorders. Furthermore, fibrinogen is well-suited as a model for studying structure-function relationships in a multi-functional protein, as it interacts in a highly specific way with a number of proteins, with cell surface receptors, and with certain ions.

Brown, J.H., Volkmann, N., Jun, G., Henschen-Edman, A.H., and Cohen, C. (2000) The crystal structure of modified bovine fibrinogen. Proc. Natl. Acad. Sci. USA, 97, 85-90.

Henschen-Edman, A.H. (1999) On the identification of beneficial and detrimental molecular forms of fibrinogen. Haemost. 29, 179-186.

Henschen-Edman, A.H., Theodor, I., Edwards, B.F.P., and Pirkle, H. (1999) Crotalase, a fibrinogen-clotting snake venom enzyme: primary structure and evidence for a fibrinogen recognition exosite different from thrombin. Thromb. Haemost., 81, 81-86.

Henschen-Edman, A.H. (1997) Photo-oxidation of histidine as a probe for aminoterminal conformational changes during fibrinogen-fibrin conversion. Cell. Molec. Life Sci. 53, 28-32.

Henschen, A.H. (1993) Human fibrinogen - structural variants and functional sites. Thromb. Haemost. 70, 42-47.

Biotechnology

Protein Engineering

Structural Biology and Molecular Biophysics

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https://faculty.uci.edu/profile/?facultyId=2489

Last updated
08/18/2000