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Scientific Overview Research Interest Summary Principal Investigators Emeritus Faculty Recent Publications
Loren Day, Ph.D.

Research Summary  |  Selected Publications  |  C.V.

Public Health Research Institute Center
New Jersey Medical School - Rutgers, The State University of New Jersey
225 Warren Street
Newark, New Jersey 07103

Phone: (917) 647-0867
e-mail: lorenday@icloud.com

Research Summary

We are studying protein-nucleic acid interactions that occur in the assembly pathways and structures of some of the innumerable filamentous circular single-stranded DNA bacteriophages that comprise the genus Inovirus. The many characterized species are all about 7 nm in diameter, yet vary in length from 700 nm to 3700 nm depending on the size of the genome and its conformation within the core of its cylindrical capsid. The capsid cylinder is made of thousands of copies of a small protein, the major coat protein, and at the ends, where the packaged genome folds back on itself, are a few copies each of key proteins required for assembly and extrusion, and subsequent infection of the next cell. Virtually all inoviruses are integrative phages or are phylogenitically related integrative phages, in which the phage genome is integrated into the host genome. Several such filamentous phage genomes carry virulence factors, such as toxins, in strains of bacteria implicated in human diseases such as cholera, cystic fibrosis, acute gastroenteritis, neonatal meningitis, gonorrhea, and plague. Integrative filamentous phages exhibit both virulent infectious states and latent prophage states, neither of which causes cell lysis. Both states are therefore carrier states in which the infected bacterial host remains viable, so that vertical transfer of inoviruses genes to progeny bacteria always occurs. In addtion, horizontal gene transfer through released inoviruses also occurs widely, as is increasingly evident through genomic analyses. In virulent productive infections, the assemby and extrusion of virions occurs at the membrane, and Infection of the next host involves surface receptor mediated coat protein uptake into the new membrane as well as DNA uptake into the cytoplasm. The deposition of coat protein into the membrane during infection, and tranfer from the membrane during assembly, might seem to be simple reverse processes but they require many different host and viral functions. The slender filamentous phage virions are remarkably protective of their DNA against extremes of environmental conditions, yet they are efficiently assembled by the producing cell and efficiently disassembled by the target cell. The diversity of sequence and life style within the genus provides many instances in which the same function is carried out differently, with different structural symmetry patterns, stoichiometric relations, and molecular forces.

A major focus has been on DNA packaging. In each phage the DNA is present as a helix of two anti-parallel strands within the cylindrical array of overlapping -helical subunits. Dramatic differences between species occur in the details of structure and forces involved. In Pf1 there is one protein subunit for every nucleotide, and the capsid and DNA are matched in a way that holds the DNA in a highly stretched and highly twisted conformation, perhaps at the physically possible limits of stretch and twist. The sugar phosphate backbones are intertwined at the center and the bases are exposed for contact with the capsid, as indicated by extensive data from electronic, vibrational, and nuclear magnetic resonance spectroscopies, as well as from X-ray and neutron diffraction. In contrast, physico-chemical data for Ff (M13, fd, f1) show that it has a non-integer nucleotide/subunit ratio near 2.4, DNA and capsid of differing symmetries, and a right-handed DNA helix with stacked and H-bonded bases at the center and the phosphates at the interface with the capsid. The DNA structures in Xf, C2 and X phages are closely similar to each other and to this one in Ff, even though their protein shells differ significantly from each other and from the Ff capsid in terms of helical symmetry, subunit sequence, and stoichiometric nucleotide/subunit ratio. Another entirely different DNA helix is in the Pf3 phage, where the phosphates appear to surround a hole down the virus axis, with bases further outside in contact with the capsid. The inside-out DNA heliix proposed for Pf3 DNA is far less twisted and stretched than the inside-out Pf1 DNA helix. It seems clear that the internal structures of these virion are very different even though the functions are the same. It is also seems clear that fundamental issues of DNA-protein interactions can be fruitfully addressed through comparative studies of a variety of processes involved in the life cycles of Inoviruses.

Selected Publications

Sergeyev IV, Day LA, Goldbourt A, McDermott AE (2011) Chemical shifts for the unusual DNA structure in Pf1 bacteriophage from dynamic-nuclear-polarization-enhanced solid-state NMR spectroscopy. J Am Chem Soc 133: 20208-20217. PMI: 21854063

Goldbourt A, Day LA, McDermott AE (2010) Intersubunit hydrophobic interactions in Pf1 filamentous phage. J Biol Chem 285: 37051-37059. PMI: 20736177

Campos EI, Fillingham J, Li G, Zheng H, Voigt P, Kuo WH, Seepany H, Gao Z, Day LA, Greenblatt JF, Reinberg D (2010) The program for processing newly synthesized histones H3.1 and H4. Nat Struct Mol Biol 17: 1343-1351. PMI: 20953179

Kalinina J, Byron SA, Makarenkova HP, Olsen SK, Eliseenkova AV, Larochelle WJ, Dhanabal M, Blais S, Ornitz DM, Day LA, Neubert TA, Pollock PM, Mohammadi M (2009) Homodimerization controls the fibroblast growth factor 9 subfamily's receptor binding and heparan sulfate-dependent diffusion in the extracellular matrix. Mol Cell Biol 29: 4663-4678. PMI: 19564416

Lorieau JL, Day LA, McDermott AE (2008) Conformational dynamics of an intact virus: order parameters for the coat protein of Pf1 bacteriophage. Proc Natl Acad Sci U S A 105: 10366-10371. PMI: 18653759

Day LA (2008) In Mahy BWJ and van Regenmortel MHV (eds.), Encyclopedia of Virology 3rd Edition in 5 Vols ed. Elsevier, Oxford, pp. 117-124.

Tomar S, Green MM, Day LA (2007) DNA-protein interactions as the source of large-length-scale chirality evident in the liquid crystal behavior of filamentous bacteriophages. J Am Chem Soc 129: 3367-3375. PMI: 17316002

Goldbourt A, Gross BJ, Day LA, McDermott AE (2007) Filamentous phage studied by magic-angle spinning NMR: resonance assignment and secondary structure of the coat protein in Pf1. J Am Chem Soc 129: 2338-2344. PMI: 17279748

Goldbourt A, Day LA, McDermott AE (2007) Assignment of congested NMR spectra: carbonyl backbone enrichment via the Entner-Doudoroff pathway. J Magn Reson 189: 157-165. PMI: 17900951

Blanch EW, Hecht L, Day LA, Pederson DM, Barron LD (2001) Tryptophan absolute stereochemistry in viral coat proteins from raman optical activity. J Am Chem Soc 123: 4863-4864. PMI: 11457308

Blanch EW, Bell AF, Hecht L, Day LA, Barron LD (1999) Raman optical activity of filamentous bacteriophages: hydration of alpha-helices. J Mol Biol 290: 1-7. PMI: 10388553

Kostrikis LG, Reisberg SA, Kim HY, Shin S, Day LA (1995) C2, and unusual filamentous bacterial virus: protein sequence and conformation, DNA size and conformation, and nucleotide/subunit ratio. Biochemistry 34: 4077-4087. PMI: 7696272

Marzec CJ, Day LA (1994) An electrostatic spatial resonance model for coaxial helical structures with applications to the filamentous bacteriophages. Biophys J 67: 2205-2222. PMI: 7696463

Arnold GE, Day LA, Dunker AK (1992) Tryptophan contributions to the unusual circular dichroism of fd bacteriophage. Biochemistry 31: 7948-7956. PMI: 1510981

Kostrikis LG, Reisberg SA, Simon MN, Wall JS, Day LA (1991) Export of infectious particles by Escherichia coli transfected with the RF DNA of Pf1, a virus of Pseudomonas aeruginosa strain K. Mol Microbiol 5: 2641-2647. PMI: 1779755

Thomas GJ, Jr., Prescott B, Opella SJ, Day LA (1988) Sugar pucker and phosphodiester conformations in viral genomes of filamentous bacteriophages: fd, If1, IKe, Pf1, Xf, and Pf3. Biochemistry 27: 4350-4357. PMI: 3166982

Marzec CJ, Day LA (1988) A theory of the symmetries of filamentous bacteriophages. Biophys J 53: 425-440. PMI: 3349133

Day LA, Marzec CJ, Reisberg SA, Casadevall A (1988) DNA packing in filamentous bacteriophages. Annu Rev Biophys Biophys Chem 17: 509-539. PMI: 3293598

Day LA, Casadevall A, Prescott B, Thomas GJ, Jr. (1988) Raman spectroscopy of mercury (II) binding to two filamentous viruses: Ff (fd, M13, f1) and Pf1. Biochemistry 27: 706-711. PMI: 3280025

Casadevall A, Day LA (1988) Thermal difference circular dichroism of Pf1 filamentous virus and effects of mercury(II), silver(I), and copper(II). Biochemistry 27: 3599-3602. PMI: 3136800

Luiten RG, Putterman DG, Schoenmakers JG, Konings RN, Day LA (1985) Nucleotide sequence of the genome of Pf3, an IncP-1 plasmid-specific filamentous bacteriophage of Pseudomonas aeruginosa. J Virol 56: 268-276. PMI: 3928901

Casadevall A, Day LA (1985) The precursor complex of Pf3 bacteriophage. Virology 145: 260-272. PMI: 3927586

Putterman DG, Casadevall A, Boyle PD, Yang HL, Frangione B, Day LA (1984) Major coat protein and single-stranded DNA-binding protein of filamentous virus Pf3. Proc Natl Acad Sci U S A 81: 699-703. PMI: 6422463

Thomas GJ, Jr., Prescott B, Day LA (1983) Structure similarity, difference and variability in the filamentous viruses fd, If1, IKe, Pf1 and Xf. Investigation by laser Raman spectroscopy. J Mol Biol 165: 321-356. PMI: 6405045

Casadevall A, Day LA (1983) Silver and mercury probing of deoxyribonucleic acid structures in the filamentous viruses fd, If1, IKe, Xf, Pf1, and Pf3. Biochemistry 22: 4831-4842. PMI: 6354268

Peterson C, Winter WT, Dalack GW, Day LA (1982) Structure of the filamentous bacteriophage, Pf3, by X-ray fiber diffraction. J Mol Biol 162: 877-881. PMI: 7169637

Newman J, Day LA, Dalack GW, Eden D (1982) Hydrodynamic determination of molecular weight, dimensions, and structural parameters of Pf3 virus. Biochemistry 21: 3352-3358. PMI: 7115675

Casadevall A, Day LA (1982) DNA packing in the filamentous viruses fd, Xf, Pf1 and Pf3. Nucleic Acids Res 10: 2467-2481. PMI: 6806774

Day LA, Mindich L (1980) The molecular weight of bacteriophage phi 6 and its nucleocapsid. Virology 103: 376-385. PMI: 7385585

Chen FC, Koopmans G, Wiseman RL, Day LA, Swinney HL (1980) Dimensions of Xf virus from its rotational and translational diffusion coefficients. Biochemistry 19: 1373-1376. PMI: 7387996

Berkowitz SA, Day LA (1980) Turbidity measurements in an analytical ultracentrifuge. Determinations of mass per length for filamentous viruses fd, Xf, and Pf3. Biochemistry 19: 2696-2702. PMI: 6994796

Day LA, Wiseman RL, Marzec CJ (1979) Structure models for DNA in filamentous viruses with phosphates near the center. Nucleic Acids Res 7: 1393-1403. PMI: 503855

Renz M, Day LA (1976) Transition from noncooperative to cooperative and selective binding of histone H1 to DNA. Biochemistry 15: 3220-3228. PMI: 782515

Pretorius HT, Klein M, Day LA (1975) Gene V protein of fd bacteriophage. Dimer formation and the role of tyrosyl groups in DNA binding. J Biol Chem 250: 9262-9269. PMI: 1194281

Camerini-Otero RD, Franklin RM, Day LA (1974) Molecular weights, dispersion of refractive index increments, and dimensions from transmittance spectrophotometry. Bacteriophages R17, T7, and PM2, and tobacco mosaic virus. Biochemistry 13: 3763-3773. PMI: 4853250

Day LA (1973) Circular dichroism and ultraviolet absorption of a deoxyribonucleic acid binding protein of filamentous bacteriophage. Biochemistry 12: 5329-5339. PMI: 4586518

Day LA, Franklin RM, Pettersson U, Philipson L (1972) Optical properties of the hexon of adenovirus. Eur J Biochem 29: 537-541. PMI: 5083509

Day LA (1969) Conformations of single-stranded DNA and coat protein in fd bacteriophage as revealed by ultraviolet absorption spectroscopy. J Mol Biol 39: 265-277. PMI: 5362671

Day LA (1966) Protein conformation in fd bacteriophage as investigated by optical rotatory dispersion. J Mol Biol 15: 395-398. PMI: 5912051


Education and academic appointments: Oberlin College, B.A., 1958;
Yale University, Ph.D., 1963;
Max Planck Institute, Germany, NIH Postdoctoral Fellow, 1964-1968;
PHRI, Assitant, Associate, and Full Member, 1968-present;
New York University School of Medicine, Faculty, 1969-present.

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