Harold P. Erickson, Ph.D. (Johns Hopkins University)
James B. Duke Professor,
Department of Cell Biology
Programs: Cell and Molecular Biology, Structural Biology and Biophysics
412 Nanaline Duke Bldg., Box 3709
Duke University Medical Center
Durham, NC 27710
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.
Erickson HP. (2017) The discovery of the prokaryotic cytoskeleton: 25th anniversary. Mol Biol Cell. 1;28(3):357-358.
Chen Y, Porter K, Osawa M, Augustus AM, Milam SL, Joshi C, Osteryoung KW, Erickson HP. (2017) The Chloroplast Tubulin Homologs FtsZA and FtsZB from the Red Alga Galdieria sulphuraria Co-assemble into Dynamic Filaments. J Biol Chem.
Shah R, Ohashi T, Erickson HP, Oas TG. (2017) Spontaneous Unfolding-Refolding of Fibronectin Type III Domains Assayed by Thiol Exchange: Thermodynamic Stability Correlates With Rates of Unfolding Rather Than Holding. J Biol Chem. 20;292(3):955-966.
Suzuki A, Badger BL, Haase J, Ohashi T, Erickson HP, Salmon ED, Bloom K. (2016) How the kinetochore couples microtubule force and centromere stretch to move chromosomes. Nat Cell Biol. 18(4):382-92.
Mansour RG, Stamper L, Jaeger F, McGuire E, Fouda G, Amos J, Barbas K, Ohashi T, Alam SM, Erickson H, Permar SR. (2016) The Presence and Anti-HIV-1 Function of Tenascin C in Breast Milk and Genital Fluids. PLoS One. 16;11(5):e0155261.
Housman M, Milam SL, Moore DA, Osawa M, Erickson HP. (2016) FtsZ Protofilament Curvature Is the Opposite of Tubulin Rings. Biochemistry. 26;55(29):4085-91.
Moore DA, Whatley ZN, Joshi CP, Osawa M, Erickson HP. (2016) Probing for Binding Regions of the FtsZ Protein Surface through Site-Directed Insertions: Discovery of Fully Functional FtsZ-Fluorescent Proteins. J Bacteriol. 13;199(1).
Erickson HP. (2016) Protein unfolding under isometric tension-what force can integrins generate, and can it unfold FNIII domains? Curr Opin Struct Biol. 27;42:98-105.
Bisson-Filho AW, Discola KF, Castellen P, Blasios V, Martins A, Sforça ML, Garcia W, Zeri AC, Erickson HP, Dessen A, Gueiros-Filho FJ (2015) FtsZ filament capping by MciZ, a developmental regulator of bacterial division. Proc Natl Acad Sci USA 112(17):E2130-8.
Albrecht E, Norheim F, Thiede B, Holen T, Ohashi T, Schering L, Lee S, Brenmoehl J, Thomas S, Drevon CA, Erickson HP, Maak S (2015) Irisin - a myth rather than an exercise-inducible myokine. Sci Rep 5:8889