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Pamela Björkman

Björkman research images. Click image for full size and description.

Pamela Björkman returns to MCB on Thursday, June 2nd, to deliver the 20th Konrad Bloch Lecture.  Björkman’s research at Caltech has focused on the structure and function of proteins involved in cell surface recognition in immunity, an interest sparked by her graduate work.  Björkman received her PhD in biochemistry from Harvard University in 1984.  As a graduate student and later a postdoctoral fellow in Don Wiley’s lab, Björkman, in collaboration with Jack Strominger, determined the crystal structure of the class I major histocompatibility complex (MHC) molecule HLA-A2.  The structure elucidated the mechanism of antigen presentation by these class I molecules.  A groove at the top of the class I molecule, formed by two long α-helices, displayed the now famous “extra density”, which was attributed to bound peptide antigens.  The two resulting publications in Nature are widely considered landmark papers in structural biology and immunology.  Björkman and Wiley won the 1994 Gairdner Foundation International Award for this work.  Upon leaving Harvard, Björkman first did a postdoctoral fellowship with Mark Davis at Stanford, working on T cell receptors.  Björkman then joined the faculty at Caltech in 1989, where she now is the Max Delbrück Professor of Biology and Howard Hughes Medical Institute (HHMI) Investigator. 

The Björkman laboratory continues to study the structural biology of cell surface recognition and is particularly interested in the structure and function of structural homologs of class I MHC molecules.  For example, crystal structures elucidated how the neonatal Fc receptor uses its class I-like fold to bind IgG molecules.  The Fc receptor causes the transfer of maternal IgG molecules to the fetus to transfer immunity to the neonate.  Another class I-like molecule of interest in the Björkman lab is HFE, which is defective in human hereditary hemochromatosis, an iron metabolism disease causing iron overload.  Björkman studies the interactions of HFE with the transferrin receptor, and how it affects binding of transferrin and iron uptake by cells.  Yet another example of a class I-like molecule is the Zn-α2-glycoprotein (ZAG), which has been implicated in cachexia, a wasting syndrome affecting terminally ill patients.  Structures determined in the Björkman lab showed how ZAG binds non-peptide ligands in its hydrophobic groove.

A recurring theme in Björkman’s research is therefore the class I MHC fold, and her work has highlighted the diversity of functions performed by these class I-like molecules.  However, as a true structural biologist, the static pictures provided by x-ray crystallography are often only the beginning of Björkman’s studies.  The crystal structures are followed by biochemical and biophysical analyses of the proteins and their interactions with biological ligands.  More recently, Björkman’s research is moving to a larger scale, using electron microscopy and confocal imaging of HFE and the Fc receptor at work inside cells.  The combination of molecular and cell-based techniques will likely yield many more insights into the biological mechanisms of these proteins.

Konrad Bloch
Pamela Björkman’s work has been recognized by numerous awards.  Notably, she is a member of the American Academy of Arts and Sciences, the National Academy of Sciences and the American Philosophical Society.  Her Bloch lecture is titled “Immunoglobulin Receptor Structure and Function from Molecules to Cells”.  The lecture, sponsored by Pfizer, honors Harvard faculty member and Nobel-prize recipient Konrad Bloch (1912-2000), a pioneer in the field of cholesterol and lipid metabolism.