(Biophysics, Johns Hopkins University)
B. Duke Professor,
Department of Cell Biology
Programs: CMB, Molecular Biophysics
Cytoskeleton: It is now clear that the actin and microtubule cytoskeleton originated in bacteria. Our major research is on FtsZ, the bacterial tubulin homolog, which assembles into a contractile ring that divides the bacterium. We have studied FtsZ assembly in vitro, and found that it assembles into thin protofilaments. Dozens of these protofilaments are further clustered to form the contractile Z-ring in vivo. Recent discoveries include:
• The Z ring is very dynamic, exchanging subunits with a half time of 8 s.
• Reconstitution of Z rings in vitro. We provided FtsZ with a membrane tether, and found that when incorporated inside liposomes, membrane-targeted FtsZ can assemble Z rings without any other proteins.
• These reconstituted Z rings can also generate a constriction force on the membranes, again without any other proteins (no motor molecules).
• The constriction force is generated by a curved conformation of the protofilaments generating a bending force on the membrane.
• Negative stain EM of artificial Z rings shows ribbons of protofilaments, contradicting the prevailing view from cryoEM tomography of scattered protofilaments
Our long term goals are two-fold. First, to understand the mechanism of bacterial cell division. Second, to learn basic principles of assembly and mechanics that will apply to both FtsZ and tubulin.
Extracellular Matrix: A second interest of our lab is extracellular matrix and cell adhesion, focusing now on fibronectin. We have discovered that the FN matrix is very elastic, with fibrils stretching up to four-fold over their relaxed length. We have two possible mechanisms to explain the elasticity of FN, and are currently developing experimental tests to resolve the mechanism. We are also studying the molecular structure of FN matrix fibrils and the mechanism of assembly. Assembly of "super FN" is providing important new insights.
412 Nanaline Duke Bldg., Box 3709
Duke University Medical Center
Durham, NC 27710
publications, and some e-prints (pdfs)
Osawa, M., and H.P. Erickson. 2011. Inside-out Z rings - constriction with and without GTP hydrolysis. Molecular microbiology. 81:571-579.
Lemmon, C.A., T. Ohashi, and H.P. Erickson. 2011. Probing the folded state of fibronectin type-III domains in stretched fibrils by measuring buried cysteine accessibility. The Journal of biological chemistry.
Osawa, M., D.E. Anderson, and H.P. Erickson. 2008. Reconstitution of contractile FtsZ rings in liposomes. Science. 320:792-4.
Ohashi T, Galiacy SD, Briscoe G, Erickson HP. An experimental
study of GFP-based FRET, with application to intrinsically
unstructured proteins. Protein Sci 2007;16(7):1429-38.
Erickson HP. Evolution of the cytoskeleton. Bioessays
Chen Y, Erickson HP. Rapid in vitro assembly dynamics
and subunit turnover of FtsZ demonstrated by fluorescence
resonance energy transfer. J. Biol. Chem. 2005;280:22549-22554.
Anderson DE, Gueiros-Filho FJ, Erickson HP. Assembly
Dynamics of FtsZ Rings in Bacillus subtilis and Escherichia
coli and Effects of FtsZ-Regulating Proteins. J Bacteriol
Erickson HP. Gene knockouts of c-src, TGF-beta1, and
tenascin suggest superfluous, non-functional expression
of proteins. Journal of Cell Biology 1993;120:1079-1081.
Projects and Lab Personnel
Tomoo Ohashi (Assistant Research Professor): Fibronectin matrix assembly
Masaki Osawa (Assistant Research Professor): FtsZ rings in liposomes - towards reconstituting cell division in vitro.
Sara Milam (Postdoc): In vitro assembly of FtsZ from chloroplasts and various bacteria.
Kiani Arkus (Grad Student): The tail of FtsZ; finding suppressor mutations by Solexa sequencing.
Max Housman (Grad Student): Super-resolution light microscopy of FtsZ and fibronectin.
Desmond Moore (Biochemistry Grad Student): Discovery of fully functional FtsZ-YFP – internal inserts.
Riddhi Shah (Biochemistry Grad Student): Determining the protein-protein bonds in fibronectin matrix fibrils, using chemical crosslinking and mass spec.
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