Les Burtnick

Faculty Directory Header Image

Les Burtnick

Profile

Research and Teaching Interests

Actin (View 3hbt) is involved in several aspects of maintaining the circulation of blood, from its contractile function in cardiac and vascular muscles to its role in the motility of white blood cells. Gelsolin is found in circulating cells such as platelets and macrophages. It is a regulator of actin filament assembly and disassembly. Its actin-binding ability is sensitive to and may be regulated by variations in levels of calcium ions or phosphatidyl inositol metabolites. Gelsolin in plasma prevents viscosity-related problems that would occur should cellular stores of actin be released into the circulation as a result of cell death due to injury or disease. The vitamin D binding and carrier protein (DBP) in plasma also aids in clearance of actin from the circulation.

We have grown crystals of intact plasma gelsolin and have solved its three dimensional structure in a calcium-free state using x-ray diffraction methods (View 1d0n). The protein consists of six independently folded but structurally similar domains that interact with each other to give a relatively compact, globular appearance. We also have determined the structures of several large fragments of calcium-activated gelsolin, including those of both the N- and the C-terminal halves of gelsolin, respectively (View 1rgi, View 1h1v), each bound to an actin monomer. These structures allow us to model how interaction with calcium ions might activate gelsolin to carry out its actin capping, severing and nucleating functions. We are working to solve the structure of fully activated, whole gelsolin bound to actin. Throughout this work, I have enjoyed a long and productive collaboration with Dr. Robert Robinson, now at the Institute of Molecular and Cell Biology, Singapore. 

Contact

Real name: 
Email: 

Curriculum Vitae

B.Sc., Manitoba (1972); Ph.D., Alberta (C.M. Kay, 1977); Postdoctoral, Weizmann Institute (I. Z. Steinberg, 1977-78); Sabbatical leaves, Alberta (L.B. Smillie, 1983-84), Oxford (E.Y. Jones and D. Stuart, 1994-95), Uppsala (R.C. Robinson, 2002-2003), Singapore (IMCB, R.C. Robinson, 2012); Retired, 2014.

Publications

2015

Van Overbeke, W. ; Wongsantichon, J. ; Everaert, I. ; Verhelle, A. ; Zwaenepoel, O. ; Loonchanta, A. ; Burtnick, L. D. ; De Ganck, A. ; Hochepied, T. ; Haigh, J. ; Cuvelier, C. ; Derave, W. ; Robinson, R. C. ; Gettemans, J. An Er-Directed Gelsolin Nanobody Targets The First Step In Amyloid Formation In A Gelsolin Amyloidosis Mouse Model. Human Molecular Genetics 2015, 24, 2492-2507.

2014

Lv, C. ; Gao, X. ; Li, W. ; Xue, B. ; Qin, M. ; Burtnick, L. D. ; Zhou, H. ; Cao, Y. ; Robinson, R. C. ; Wang, W. Single-Molecule Force Spectroscopy Reveals Force-Enhanced Binding Of Calcium Ions By Gelsolin. Nature Communications 2014, 5:4623.
Bellac, C. L. ; Dufour, A. ; Krisinger, M. J. ; Loonchanta, A. ; Starr, A. E. ; auf-dem-Keller, U. ; Lange, P. F. ; Goebeler, V. ; Kappelhoff, R. ; Butler, G. S. ; Burtnick, L. D. ; Conway, E. M. ; Roberts, C. R. ; Overall, C. M. Macrophage Matrix Metalloproteinase-12 Dampens Inflammation And Neutrophil Influx In Arthritis. Cell Reports 2014, 9, 618-632.

2013

Nag, S. ; Larsson, M. ; Robinson, R. C. ; Burtnick, L. D. Gelsolin: The Tail Of A Molecular Gymnast. Cytoskeleton (Hoboken, N.J.) 2013, 70, 360-84.
Ghoshdastider, U. ; Popp, D. ; Burtnick, L. D. ; Robinson, R. C. The Expanding Superfamily Of Gelsolin Homology Domain Proteins. Cytoskeleton 2013, 70, 775-795.

2010

Wang, H. ; Robinson, R. C. ; Burtnick, L. D. The Structure Of Native G-Actin. Cytoskeleton 2010, 67, 456 - 465.

2009

Nag, S. ; Ma, Q. ; Wang, H. ; Chumnarnsilpa, S. ; Lee, W. L. ; Larsson, M. ; Kannan, B. ; Hernandez-Valladarez, M. ; Burtnick, L. D. ; Robinson, R. C. Ca2+ Binding By Domain 2 Plays A Critical Role In The Activation And Stabilization Of Gelsolin. Proceedings of the National Academy of Sciences of the United States of America 2009, 106, 13713-13718.
Chumnarnsilpa, S. ; Lee, W. L. ; Nag, S. ; Kannan, B. ; Larsson, M. ; Burtnick, L. D. ; Robinson, R. C. The Crystal Structure Of The C-Terminus Of Adseverin Reveals The Actin-Binding Interface. Proceedings of the National Academy of Sciences of the United States of America 2009, 106, 13719-13724.
Wang, H. ; Chumnarnsilpa, S. ; Loonchanta, A. ; Li, Q. ; Kuan, Y. M. ; Robine, S. ; Larsson, M. ; Mihalek, I. ; Burtnick, L. D. ; Robinson, R. C. Helix Straightening As An Activation Mechanism In The Gelsolin Superfamily Of Actin Regulatory Proteins. Journal of Biological Chemistry 2009, 284, 21265-21269.

2007

Zaccai, N. R. ; May, A. P. ; Robinson, R. C. ; Burtnick, L. D. ; Crocker, P. R. ; Brossmer, R. ; Keim, S. ; Jones, E. Y. Crystallographic And In Silico Analysis Of The Sialoside-Binding Characteristics Of The Siglec Sialoadhesin. Journal of Molecular Biology 2007, 365, 1469-1479.

2006

Chumnarnsilpa, S. ; Loonchanta, A. ; Xue, B. ; Choe, H. ; Urosev, D. ; Wang, H. ; Lindberg, U. ; Burtnick, L. D. ; Robinson, R. C. Calcium Ion Exchange In Crystalline Gelsolin. Journal of Molecular Biology 2006, 357, 773-782.
Urosev, D. ; Ma, Q. ; Tan, A. L. C. ; Robinson, R. C. ; Burtnick, L. D. The Structure Of Gelsolin Bound To Atp. Journal of Molecular Biology 2006, 357, 765-772.

2005

Aguda, A. H. ; Burtnick, L. D. ; Robinson, R. C. The State Of The Filament. Embo Reports 2005, 6, 220-226.

2004

Irobi, E. ; Aguda, A. H. ; Larsson, M. ; Guerin, C. ; Yin, H. L. ; Burtnick, L. D. ; Blanchoin, L. ; Robinson, R. C. Structural Basis Of Actin Sequestration By Thymosin-Beta 4: Implications For Wh2 Proteins. Embo Journal 2004, 23, 3599-3608.
Burtnick, L. D. ; Urosev, D. ; Irobi, E. ; Narayan, K. ; Robinson, R. C. Structure Of The N-Terminal Half Of Gelsolin Bound To Actin: Roles In Severing, Apoptosis And Faf. Embo Journal 2004, 23, 2713-2722.

2003

Narayan, K. ; Chumnarnsilpa, S. ; Choe, H. ; Irobi, E. ; Urosev, D. ; Lindberg, U. ; Schutt, C. E. ; Burtnick, L. D. ; Robinson, R. C. Activation In Isolation: Exposure Of The Actin-Binding Site In The C-Terminal Half Of Gelsolin Does Not Require Actin. Febs Letters 2003, 552, 82-85.
Irobi, E. ; Burtnick, L. D. ; Urosev, D. ; Narayan, K. ; Robinson, R. C. From The First To The Second Domain Of Gelsolin: A Common Path On The Surface Of Actin?. Febs Letters 2003, 552, 86-90.

2002

Choe, H. ; Burtnick, L. D. ; Mejillano, M. ; Yin, H. L. ; Robinson, R. C. ; Choe, S. The Calcium Activation Of Gelsolin: Insights From The 3 Angstrom Structure Of The G4-G6/actin Complex. Journal of Molecular Biology 2002, 324, 691-702.

2001

Robinson, R. C. ; Choe, S. Y. ; Burtnick, L. D. The Disintegration Of A Molecule: The Role Of Gelsolin In Faf, Familial Amyloidosis (Finnish Type). Proceedings of the National Academy of Sciences of the United States of America 2001, 98, 2117-2118.

1999

Robinson, R. C. ; Mejillano, M. ; Le, V. P. ; Burtnick, L. D. ; Yin, H. L. ; Choe, S. Domain Movement In Gelsolin: A Calcium-Activated Switch. Science 1999, 286, 1939-1942.
Robinson, R. C. ; Radziejewski, C. ; Spraggon, G. ; Greenwald, J. ; Kostura, M. R. ; Burtnick, L. D. ; Stuart, D. I. ; Choe, S. ; Jones, E. Y. The Structures Of The Neurotrophin 4 Homodimer And The Brain-Derived Neurotrophic Factor/neurotrophin 4 Heterodimer Reveal A Common Trk-Binding Site. Protein Science 1999, 8, 2589-2597.

1998

Koepf, E. K. ; Hewitt, J. ; Vo, H. ; MacGillivray, R. T. A. ; Burtnick, L. D. Equus Caballus Gelsolin - Cdna Sequence And Protein Structural Implications. European Journal of Biochemistry 1998, 251, 613-621.

1997

Burtnick, L. D. ; Koepf, E. K. ; Grimes, J. ; Jones, E. Y. ; Stuart, D. I. ; McLaughlin, P. J. ; Robinson, R. C. The Crystal Structure Of Plasma Gelsolin: Implications For Actin Severing, Capping, And Nucleation. Cell 1997, 90, 661-670.

1996

Burtnick, L. D. ; Robinson, R. C. ; Koepf, E. K. The Structure Of Horse Plasma Gelsolin To 2.5 Angstrom. Biophysical Journal 1996, 70, SUA12-SUA12.
Koepf, E. K. ; Burtnick, L. D. Multiple Pathways For Denaturation Of Horse Plasma Gelsolin. Biochemistry and Cell Biology-Biochimie Et Biologie Cellulaire 1996, 74, 101-107.

1994

Din, N. ; Forsythe, I. J. ; Burtnick, L. D. ; Gilkes, N. R. ; Miller, R. C. ; Warren, R. A. J. ; Kilburn, D. G. The Cellulose-Binding Domain Of Endoglucanase-A (Cena) From Cellulomonas-Fimi - Evidence For The Involvement Of Tryptophan Residues In Binding. Molecular Microbiology 1994, 11, 747-755.

1993

Koepf, E. K. ; Burtnick, L. D. Horse Plasma Gelsolin Labeled With Fluorescein Isothiocyanate Responds To Calcium And Actin. European Journal of Biochemistry 1993, 212, 713-718.
Reid, S. W. ; Koepf, E. K. ; Burtnick, L. D. Fluorescent Responses Of Acrylodan-Labeled Plasma Gelsolin. Archives of Biochemistry and Biophysics 1993, 302, 31-36.
Koepf, E. K. ; Burtnick, L. D. Thermal-Stability Of Fitc-Labeled Plasma Gelsolin. Faseb Journal 1993, 7, A1287-A1287.

1992

Silva, B. E. R. ; Koepf, E. K. ; Burtnick, L. D. ; Turro, N. J. Monomer And Excimer Fluorescence Of Horse Plasma Gelsolin Labeled With N-(1-Pyrenyl)Iodoacetamide. Biochemistry and Cell Biology-Biochimie Et Biologie Cellulaire 1992, 70, 573-578.
Robinson, R. C. ; Burtnick, L. D. Stabilization Of The Structure Of Horse Plasma Vitamin-D Binding-Protein By Disulfide Bonds. Biochemistry and Cell Biology-Biochimie Et Biologie Cellulaire 1992, 70, 10-15.
Koepf, E. K. ; Burtnick, L. D. Interaction Of Plasma Gelsolin With Tropomyosin. Febs Letters 1992, 309, 56-58.

1991

Clark, I. D. ; Burtnick, L. D. Hybridization Of Rabbit Cardiac Tropomyosin With Nonpolymerizable Tropomyosin Species. Biochemistry International 1991, 23, 801-807.
Silva, B. E. R. ; Burtnick, L. D. ; Turro, N. J. Interaction Of Horse Plasma Gelsolin With The Hydrophobic Fluorescent-Probe 2-(N-Methylanilino)Naphthalene-6-Sulfonic Acid. Biochemistry International 1991, 23, 905-913.

1990

Silva, B. E. R. ; Burtnick, L. D. Characterization Of Horse Plasma Gelsolin. Biochemistry and Cell Biology-Biochimie Et Biologie Cellulaire 1990, 68, 796-800.

1989

Clark, I. D. ; Burtnick, L. D. Interaction Of Muscle And Non-Muscle Tropomyosins With Deoxyribonuclease-I. European Journal of Biochemistry 1989, 185, 105-109.
Burtnick, L. D. ; Wong, M. K. C. Interaction Of Iodoacetamidofluorescein-Labelled Tropomyosin With Deoxyribonuclease-I. Febs Letters 1989, 244, 319-322.

1988

Burtnick, L. D. ; Racic, A. A Fluorescent-Probe Study Of The Cysteine Environments In Muscle Tropomyosins. Biophysical Journal 1988, 53, A588-A588.
Burtnick, L. D. ; Racic, A. 7-Diethylamino-3-((4’-Iodoacetylamino)Phenyl)-4-Methylcoumarin, A Fluorescent-Probe Of The Hydrophobic Cleft In The Tropomyosin Coiled Coil. Canadian Journal of Chemistry-Revue Canadienne De Chimie 1988, 66, 1805-1808.
Burtnick, L. D. ; Sanders, C. ; Smillie, L. B. Fluorescence From Pyrene-Labeled Native And Reconstituted Chicken Gizzard Tropomyosins. Archives of Biochemistry and Biophysics 1988, 266, 622-627.
Burtnick, L. D. ; Clark, I. D. Fluorescence Of Acrylodan-Labelled Equine Platelet Tropomyosin. Journal of Muscle Research and Cell Motility 1988, 9, 87-87.
Clark, I. D. ; Burtnick, L. D. Fluorescence Of Equine Platelet Tropomyosin Labeled With Acrylodan. Archives of Biochemistry and Biophysics 1988, 260, 595-600.

1987

Burtnick, L. D. Quenching Of The Fluorescence Of Actin Modified At Lysine-61. Biochemistry International 1987, 14, 547-551.
Burtnick, L. D. ; Veres, L. Reaction With Dansylaziridine Blocks The Abilities Of Cardiac Tropomyosin To Polymerize And To Bind F-Actin. Journal of Cellular Biochemistry 1987, 163-163.

1986

Sanders, C. ; Burtnick, L. D. ; Smillie, L. B. Native Chicken Gizzard Tropomyosin Is Predominantly A Beta-Gamma-Heterodimer. Journal of Biological Chemistry 1986, 261, 2774-2778.
Burtnick, L. D. ; Bhangu, K. Interaction Of Actin With Dansyl-Tropomyosin. Febs Letters 1986, 198, 307-310.
Clark, I. D. ; Burtnick, L. D. Fluorescence Of Acrylodan-Labeled Platelet Tropomyosin. Biophysical Journal 1986, 49, A257-A257.

1985

Burtnick, L. D. ; Stewart, D. I. H. ; Smillie, L. B. Excimer Fluorescence From Pyrene Labeled Platelet Tropomyosin. Biophysical Journal 1985, 47, A471-A471.

1984

Burtnick, L. D. ; Isaac, C. D. Modification Of Actin With 2-(N-Methylanilino)Naphthalene-6-Sulfonyl Chloride. Canadian Journal of Biochemistry and Cell Biology 1984, 62, 191-195.
Burtnick, L. D. Modification Of Actin With Fluorescein Isothiocyanate. Biochimica Et Biophysica Acta 1984, 791, 57-62.
Burtnick, L. D. ; Chan, K. W. Properties Of Muscle Actin Labeled With Fluorescein Isothiocyanate. Biophysical Journal 1984, 45, A108-A108.

1983

Burtnick, L. D. ; Chan, K. W. Fluorescence Of Actin-Bound Hydrophobic Molecules. Canadian Journal of Biochemistry and Cell Biology 1983, 61, 981-988.
Burtnick, L. D. ; Chan, K. W. Fluorescence Of Actin-Bound Hydrophobic Probes. Biophysical Journal 1983, 41, A100-A100.

1982

Ng, J. S. Y. ; Burtnick, L. D. Chemical Modifications Of Actin - Effects On Interaction With Deoxyribonuclease-I. International Journal of Biological Macromolecules 1982, 4, 215-218.
Burtnick, L. D. Luminescence Of Actin-Bound Terbium Ions. Biophysical Journal 1982, 37, A53-A53.

1981

Burns, P. D. ; Burtnick, L. D. 400 Mhz Proton Nuclear Magnetic-Resonance Studies On Rabbit Muscle G-Actin. Biochemistry International 1981, 3, 233-237.

1980

Burtnick, L. D. ; Chan, K. W. Deoxyribonuclease-I Binding Masks The Major Tryptic Cleavage Sites On Actin. Life Sciences 1980, 26, 1323-1327.
Burtnick, L. D. ; Chan, K. W. Protection Of Actin Against Proteolysis By Complex-Formation With Deoxyribonuclease-I. Canadian Journal of Biochemistry 1980, 58, 1348-1354.