In the coming year we plan to pursue 4 lines of research: a) Electron microscopy of thin sections of fibrin. We will use tannic acid fixation in an attempt to visualize the packing of protofibrils in cross-sections of fibrin fibers. b) Electron microscopy of Factor VIII. These studies will be pursued in collaboration with Dr. P.A. McKee's lab for purification and characterization of Factor VIII. c) Electron microscopy of fibronectin. This is a serum protein closely related to the cell surface fibronectin. We have already observed the shape of the molecule (a long flexible chain) and its attachment to fibrinogen molecules. d) Nucleation and assembly of fibrinogen and fibronectin. We will use a combination light scattering and electron microscopy to characterize small polymers of these two proteins, and especially to investigate the question of nucleation of polymerization.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA047056-15
Application #
2092408
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1979-05-01
Project End
1997-11-30
Budget Start
1993-12-01
Budget End
1994-11-30
Support Year
15
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Duke University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Shah, Riddhi; Ohashi, Tomoo; Erickson, Harold P et al. (2017) Spontaneous Unfolding-Refolding of Fibronectin Type III Domains Assayed by Thiol Exchange: THERMODYNAMIC STABILITY CORRELATES WITH RATES OF UNFOLDING RATHER THAN FOLDING. J Biol Chem 292:955-966
Erickson, Harold P (2017) Protein unfolding under isometric tension-what force can integrins generate, and can it unfold FNIII domains? Curr Opin Struct Biol 42:98-105
Albrecht, Elke; Norheim, Frode; Thiede, Bernd et al. (2015) Irisin - a myth rather than an exercise-inducible myokine. Sci Rep 5:8889
Giacomodonato, Mónica N; Noto Llana, Mariángeles; Aya Castañeda, María Del Rosario et al. (2014) AvrA effector protein of Salmonella enterica serovar Enteritidis is expressed and translocated in mesenteric lymph nodes at late stages of infection in mice. Microbiology 160:1191-9
Erickson, Harold P (2013) Irisin and FNDC5 in retrospect: An exercise hormone or a transmembrane receptor? Adipocyte 2:289-93
Fouda, Genevieve G; Jaeger, Frederick H; Amos, Joshua D et al. (2013) Tenascin-C is an innate broad-spectrum, HIV-1-neutralizing protein in breast milk. Proc Natl Acad Sci U S A 110:18220-5
Schumacher, Maria A; Chinnam, Nagababu; Ohashi, Tomoo et al. (2013) The structure of irisin reveals a novel intersubunit ?-sheet fibronectin type III (FNIII) dimer: implications for receptor activation. J Biol Chem 288:33738-44
Lemmon, Christopher A; Ohashi, Tomoo; Erickson, Harold P (2011) Probing the folded state of fibronectin type III domains in stretched fibrils by measuring buried cysteine accessibility. J Biol Chem 286:26375-82
Ohashi, Tomoo; Erickson, Harold P (2011) Fibronectin aggregation and assembly: the unfolding of the second fibronectin type III domain. J Biol Chem 286:39188-99
Ohashi, Tomoo; Erickson, Harold P (2009) Revisiting the mystery of fibronectin multimers: the fibronectin matrix is composed of fibronectin dimers cross-linked by non-covalent bonds. Matrix Biol 28:170-5

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