Michael Henzl

Professor of Biochemistry

Email:	henzlm@missouri.edu
Phone:	(573) 882-7485
Lab:	(573) 882-7540
Fax:	(573) 884-4812
Office:	11C Schlundt Annex
Mailing Address:	Biochemistry 117 Schweitzer Hall University of Missouri-Columbia Columbia, MO 65211
Research Areas:	Biophysical characterization of EF-hand calcium-binding proteins; protein-ligand interactions.

Educational Background

BS		Lafayette College	Easton, Penn.	Chemistry
PhD		University of Wisconsin	Madison, Wis.	Biochemistry

Notable Honors and Service

Chair, 60th Calorimetry Conference, 2005
Scientific Program Chair, 59th Calorimetry Conference, 2004

Research Description

Ca²⁺ influences eukaryotic signal transduction via interactions with a host of Ca²⁺-binding proteins. Many of these possess a Ca²⁺-binding motif called the "EF-hand". Despite a general similarity, individual EF-hands vary in their affinity for Ca²⁺ and Mg²⁺. The basis for the variation is poorly understood. We are exploring the issue in the parvalbumins — small vertebrate-specific proteins harboring two Ca²⁺-binding sites.

The parvalbumin family includes α and β sub-lineages. Mammals express one isoform from each lineage. Interestingly, both are expressed in the sensory cells of the auditory organ (the "organ of Corti") — α in the inner hair cells (IHCs), β in the outer hair cells (OHCs). Parvalbumins are believed to serve as cytosolic Ca²⁺ buffers. It is not clear why the IHC and OHC would recruit distinct isoforms. The answer may reside in the disparate Ca²⁺-binding properties of α and β.

The Ca²⁺-binding sites in rat α behave almost identically in titrations with Ca²⁺ or Mg²⁺, exhibiting very high affinity for Ca²⁺ and substantial affinity for Mg²⁺. By contrast, the binding sites in rat β are nonequivalent and exhibit reduced affinity for divalent ions. These differences between rat α and β are especially intriguing in light of their 50% sequence identity. We are analyzing these two parvalbumins, and select site-specific variants, by titration calorimetry, differential scanning calorimetry, x-ray crystallography (with Dr. J.J. Tanner, Dept. of Chemistry), and NMR spectroscopy.

Together with researchers at Washington University in St. Louis, we are also characterizing two other proteins present in the organ of Corti (OC). OCP1 and OCP2 were discovered in 1980. Although they are the most abundant proteins in the OC, their physiological functions are unknown. They are co-expressed by the cells comprising the epithelial gap-junction system (EGJS). Having no vasculature, the OC relies heavily on the EGJS for transport of nutrients, metabolites, and signaling molecules. OCP1 and OCP2 may assist in the regulation of gap-junction activity.

OCP2 displays extreme homology to Skp1, an essential subunit in a class of ubiquitin-protein ligases known as SCF complexes. Various proteins interact with Skp1 through a sequence motif called the F-box. These "F-box proteins" also associate with specific target proteins, positioning them for modification by the ubiquitination machinery. Ubiquitination can trigger a variety of biological consequences, including proteolytic destruction.

OCP1 is an F-box protein. In accordance with prediction, it associates tightly with OCP2. The biological target protein of the putative SCF complex containing OCP1 and OCP2 is presently unknown. In vitro, OCP1 associates with connexin 26, the gene product most commonly associated with hereditary deafness disorders. Whether this interaction has any physiological relevance is currently under investigation.

Selected Publications

Henzl, M.T., and Agah, S. (2006), Divalent Ion-binding Properties of the Two Avian β-parvalbumins, Proteins 62, 270-278.

Tanner, J.J., Agah, S., Lee, Y.-H., and Henzl, M.T. (2005), Crystal Structure of the D94S/G98E Variant of Rat α-Parvalbumin. An Explanation for the Reduced Divalent Ion Affinity, Biochemistry 44, 10966-10976.

Henzl, M.T., Larson, J.D., and Agah, S. (2004), Influence of Monovalent Cation Identity on Parvalbumin Divalent Ion-Binding Properties, Biochemistry 43, 2747-2763.

Henzl, M.T., Larson, J.D., and Agah, S. (2004), Association of the AB and CD-EF Domains from Rat α- and β-Parvalbumin, Biochemistry 43, 10906-10917.

Henzl, M.T., Thalmann, I., Larson, J.D., Ignatova, E.G., and Thalmann, R. (2004), The cochlear F-box protein OCP1 forms a heterodimeric complex with OCP2 and associates with connexin 26, Hearing Res. 191, 101-109.

Employment Opportunities

Post-Doctoral Opportunities

Electronic submission is encouraged, e-mail to biochemsearch@missouri.edu

Applicants should send CV and names of two references to:
Dr. Michael Henzl
Postdoctoral Application
Biochemistry
117 Schweitzer Hall
University of Missouri-Columbia
Columbia, MO 65211

Biophysical characterization of EF-hand calcium-binding proteins; protein-ligand interactions.