Department of biochemistry and Molecular biology
Erika Bullesbach, PhD
The research interest of my laboratory is the structure and function relationship of insulin and factors of insulin-like structures. Structurally related proteo-hormones of the insulin family are the metabolic hormone insulin, the hormone of pregnancy relaxin, the testicular Leydig cell derived relaxin-like factor, and invertebrate developmental factors bombyxin (from the brains of the silk worm) and the molluscan insulin-related peptide (from neuroendocrine system of the pond snail). There is no known biological crossreactivity between these insulin-like hormones. The wide variety of biological functions inherent in essentially the same three-dimensional structure implies that the biological function of this family of proteins depends primarily on the side chain distribution. It is the goal to find the surface features that are crucial for the corresponding hormone and its interaction with its cell membrane receptor. The initial step of this investigation involves the chemical synthesis of these factors and of defined analogs. The syntheses are based upon a novel approach, the site directed disulfide-bond formation, which has been highly successful in the synthesis of insulin, relaxins, relaxin-like factor, and bombyxin. Investigation of the physical chemical and biological properties of the analogs by comparison with natural factors will give insight into their structure-function relationships. The long-term goal of these studies is that a better understanding of the mode of action of these hormones leads to the subsequent design and synthesis of mimetics. Mimetics of insulins could substitute for the daily injections of insulin-dependent diabetes, and mimetics of bombyxin may become the basis of new pest controls.
Recent Publications | Additional Publications
Pathirana IN, Kawate N, Büllesbach EE, Takahashi M, Hatoya S, Inaba T, Tamada H. (2012) Insulin-like peptide 3 stimulates testosterone secretion in mouse Leydig cells via cAMP pathway. Regul Pept 178(1-3):102-6.
Büllesbach EE and Schwabe C. (2012) Replacement of Disulfides by Amide Bonds in the Relaxin-like Factor (RLF/INSL3) Reveals a Role for the A11-B10 Link in Transmembrane Signaling. Biochemistry 51:4198-4205.
Yuan FP, Li X, Lin J, Schwabe C, Büllesbach EE, Rao CV, Lei ZM. (2010) The role of RXFP2 in mediating androgen-induced inguinoscrotal testis descent in LH receptor knockout mice. Reproduction 139(4):759-69. PMID: 20154177
Schwabe C, Büllesbach EE. (2009) The "hot wires" of the relaxin-like factor (Insl3). Ann N Y Acad Sci 1160:93-8. PMID: 19416166
Büllesbach EE, Hass MA, Jensen MR, Hansen DF, Kristensen SM, Schwabe C, Led JJ. (2008) Solution structure of a conformationally restricted fully active derivative of the human relaxin-like factor. Biochemistry 47(50):13308-17. PMID: 19086273