Contact Information

Office: Room 159

Lab: Rooms 152 and 154

Chemistry and Biochemistry Building
P.O. Box 173400
Bozeman, MT 59717

Phone: 406-994-5382

Fax: 406-994-5407




  • B.A.: University of California at San Diego, Chemistry, 1985
  • Ph.D.: Purdue University, West Lafayette, IN, Biochemistry/Biophysics 1993
  • Postdoc.: Harvard Medical School and Howard Hughes Medical Institute, X-ray Crystallography 1994/1999



Awards and Professional Activities

  • 2007-Present: Editorial Board, Journal of Biological Chemistry
  • 2009: Charles and Nora L. Wiley Award for Meritorious Research, Montana State University
  • 2003-2006: Executive Board, Thermal Biology Institute, Montana State University
  • 1998-1999: Armenise Postdoctoral Fellowship, Harvard Medical School
  • 1994-1998: Postdoctoral Fellowship, Howard Hughes Medical Institute
  • 1993: Outstanding Graduate Student, Department of Biological Sciences
  • 1990-1993: Predoctoral Fellowship, American Heart Association

Lawrence Group Overview

kid with fish

We are involved in structure-function studies on many fronts using X-ray crystallography as our primary tool. These studies are in many cases collaborations with others, both on campus and off. Focal points include: (1) Structural biology of iron transport, iron homeostasis and oxidative stress. (2) Strutural studies of hyperthermophilic viruses from Yellowstone National Park.


Structure, Biochemistry

Iron Transport and Iron Homeostasis

Iron plays an integral role in many biochemical processes essential to life. For example, iron containing metalloproteins are necessary for the synthesis of DNA, respiration and many key metabolic reactions. Thus, life as we know it is fully dependent on iron. However, the same properties that allow iron to play a central role in the chemistry of life, also lead to potentially deleterious effects. Specifically, excess Fe2+ combines with naturally occurring peroxide to produce the hydroxyl radical, one of several reactive oxygen species (ROS) that contribute to oxidative stress, reacting indiscriminately with DNA, proteins and lipids. Hence, iron levels must be carefully balanced so that enough iron is present to sustain key metabolic processes, but production of ROS are minimized. To this end, an elaborate system of transport, storage and regulatory proteins has evolved to effect iron homeostasis in humans and other organisms, including human pathogens.

Importantly, disorders of iron metabolism are among the most prevalent diseases in humans. For example, iron deficiency is thought to affect more than one billion people worldwide, and is, particularly problematic in pregnant women and young children. In addition, the anemia of inflammation, a down regulation of iron levels in response to inflammation, is the most common form of anemia in hospitalized patients, and in patients with chronic diseases such as heart failure, rheumatoid arthritis, renal disease, and cancer. Similarly, inherited iron overload disorders, collectively known as hereditary hemochromatosis, are also common. For example, the occurrence of a single disease associated allele, HFEC282Y, is as high as 10% in individuals of Northern European descent, and is the most common autosomal recessive disease currently known. In homozygous individuals, progressive iron accumulation generates oxidative stress that results in significant cellular damage, inducing inflammation and fibrosis that eventuates in hepatic cirrhosis, hepatocellular carcinoma, diabetes mellitus, cardiac insufficiency and arthropathy. In addition, excess iron and/or oxidative stress is a factor in many neurodegenerative diseases, including Parkinson’s, Huntington’s, Alzheimer’s and ALS.

Consequently, the cellular machinery responsible for iron transport and homeostasis is worthy of significant investigation, and may provide potential targets for pharmacological intervention, to either promote or inhibit systemic or cellular iron uptake, or to interfere with iron acquisition in human pathogens, where iron availability is frequently the rate limiting nutrient. In this light, we are engaged in structural studies of both human and bacterial proteins involved in iron transport and homeostasis.

Selected Publications:

Maaty WS, Wiedenheft B, Tarlykov P, Schaff N, Heinemann J, Robison-Cox J, Valenzuela J, Dougherty A, Blum P, Lawrence CM, Douglas T, Young MJ, Bothner B.:
Something old, something new, something borrowed; how the thermoacidophilic archaeon Sulfolobus solfataricus responds to oxidative stress
(2009) PLoS One. 16;4(9):e6964.

Gauss, G.H., Reott, M.A., Rocha, E.R., Young, M.J., Douglas, T., Smith, C.J. and Lawrence, C.M.:
Characterization of the Bacteroides fragilis bfr gene product reveals a DPSL protein that suggests evolutionary links in the ferritin superfamily
(Under Revision)

Sendamarai, A. K., Ohgami, R. S., Fleming, M. D., and Lawrence, C. M.:
Structure of the membrane proximal oxidoreductase domain of human Steap3, the dominant ferrireductase of the erythroid transferrin cycle.
Proceedings of the National Academy of Sciences of the United States of America (2008) 105, 7410-7415.

Gauss, G. H., Benas, P., Wiedenheft, B., Young, M., Douglas, T., and Lawrence, C. M. :
Structure of the DPS-like protein from Sulfolobus solfataricus reveals a bacterioferritin-like dimetal binding site within a DPS-like dodecameric assembly.
Biochemistry (2006) 45, 10815-10827.

Ramsay, B., Wiedenheft, B., Allen, M., Gauss, G. H., Lawrence, C. M., Young, M., and Douglas, T. :
Dps-like protein from the hyperthermophilic archaeon Pyrococcus furiosus.
Journal of Inorganic Biochemistry (2006) 100, 1061-1068.

Lawrence, C. M., Ray, S., Babyonyshev, M., Galluser, R., Borhani, D. W., and Harrison, S. C. :
Crystal structure of the ectodomain of human transferrin receptor
Science (1999) 286, 779-782.


Structure, Biochemistry


Archaeal Viruses and Virus-Host Interactions


Remarkably, viruses have been found in almost every known environment on earth, including the extreme acidic, thermal and saline environments of Yellowstone National Park where archaeal organisms are dominant. However, while more than 5,000 eukaryotic viruses and bacteriophage have been studied in detail, fewer than 50 archaeal viruses have been investigated at any level. Those, we are largely ignorant of viruses in this third domain of life. But why should we study these viruses? One reason is a growing appreciation of the roles viruses play in evolution. Remarkably with >500 cellular genomes sequenced to date, most show significant amounts of viral or viral-like sequence within their genomes, evidence that viruses play a central role in horizontal gene transfer, and have helped to drive the evolution of their hosts. Roles for viruses in cellular evolution are also being considered. Current hypotheses contend that viruses have catalyzed several major evolutionary transitions, including the invention of DNA and DNA replication mechanisms, the origin of the eukaryotic nucleus, and thus a role in the formation of the three domains of life. In addition, there is also considerable interest in viral genesis and evolution in and of itself. In order to evaluate these hypotheses and to analyze evolutionary relationships among viruses, knowledge of viruses infecting Archaea, the third domain of life, is clearly essential. A second reason to study archaeal viruses stems also from the exceptional molecular insight viruses have traditionally provided into host processes; thus studies of archaeal viruses are certain to provide new insights into the molecular biology of this poorly understood domain of life.

The hyperthermophilic Crenarchaeal viruses show incredible morphological diversity. This is accompanied by extreme genetic diversity, wherein most viral genes lack significant similarity to genes of known function. The lack of sequence similarity to genes of known function has, in turn, complicated efforts to elucidate viral life cycles, virus-host relationships, and the underlying genetics and biochemistry. We postulate, however, that many of the genes in these viruses are not unique. Rather, their encoded proteins bear remote similarities to proteins with known functions, but these similarities are masked by evolution and adaptation to extremes of temperature and pH. In this light, tertiary (3D) structural similarities between proteins persist longer on the evolutionary time scale than either primary (amino acid) or genomic sequence (DNA) similarities. Thus, we are pursuing structural studies of crenarchaeal viral proteins in order to arrive at testable functional hypotheses. Our work over the last three years clearly demonstrates the validity of this approach; protein tertiary structure does suggest function. And the insights gained from our structural studies are suggesting functions for an ever increasing number of viral proteins. These structure-function relationships are relevant not only to the viruses under study (SSVs and STIV), but for the Crenarchaea in general.

Selected Publications:

Menon, S and Lawrence C.M. :
Helix-Turn-Helix Motif
in Encyclopedia of Genetics, (2012)2nd Edition (Maloy, S. and Hughes, K., Eds.) Elsevier (In Press)

Heinemann J., Maaty W. S., Gauss G. H. , Akkaladevi N., Brumfield S. K., Rayaprolu V., Young M.J., Lawrence C.M., Bothner B.:
Fossil record of an archaeal HK97-like provirus.
Virology (2011) 417, 362-368.

Lawrence, C. M., and White, M. F. :
Recognition of archaeal CRISPR RNA; no P in the alindromic repeat?
Structure (2011) 19, 142-4

Menon S.K., Eilers B.J., Young M.J., Lawrence C.M. :
The crystal structure of D212 from sulfolobus spindle-shaped virus ragged hills reveals a new member of the PD-(D/E)XK nuclease superfamily?
J Virol. (2010) 84(12):5890-7.

Anonymous :
3D presentation of structural and image data.
J Biol Chem (2009) 284, 21101.

Fulton, J., Bothner, B., Lawrence, M., Johnson, J. E., Douglas, T., and Young, M.:
Genetics, biochemistry and structure of the archaeal virus STIV.
Biochemical Society Transactions (2009) 37, 114-117.

Lawrence, C. M., Menon, S., Eilers, B. J., Bothner, B., Khayat, R., Douglas, T., and Young, M. J.:
Structural and functional studies of archaeal viruses
J Biol Chem. (2009) 284(19):12599-12603.

Menon, S. K., Maaty, W. S., Corn, G. J., Kwok, S. C., Eilers, B. J., Kraft, P., Gillitzer, E., Young, M. J., Bothner, B., and Lawrence, C. M. :
Cysteine usage in Sulfolobus spindle-shaped virus 1 and extension to hyperthermophilic viruses in general.
Virology 376, 270-278.

Larson, E. T., Eilers, B., Menon, S., Reiter, D., Ortmann, A., Young, M. J., and Lawrence, C. M. :
A winged-helix protein from suffiblobus turreted icosahedral virus points toward stabilizing disulfide bonds in the intracellular proteins of a hyperthermophilic virus
Virology (2007) 368, 249-261.

Larson, E. T., Eilers, B. J., Reiter, D., Ortmann, A. C., Young, M. J., and Lawrence, C. M.:
A new DNA binding protein highly conserved in diverse crenarchaeal viruses
Virology (2007) 363, 387-396.

Khayat, R., Tang, L., Larson, E. T., Lawrence, C. M., Young, M., and Johnson, J. E. :
Structure of an archaeal virus capsid protein reveals a common ancestry to eukaryotic and bacterial viruses.
Proceedings of the National Academy of Sciences of the United States of America (2005) 102, 18944-18949.

Kraft, P., Gauss, G. H., Young, M., and Lawrence, C. M. :
Structural Studies of Crenarchaeal Viral Proteins: Structure Suggests Function
in Geothermal Biology and Geochemistry in Yellowstone National Park (2005) (Inskeep, W. P., and McDermot, T. R., Eds.) pp 305-316, Montana State University, Bozeman.

Kraft, P., Oeckinghaus, A., Kummel, D., Gauss, G. H., Gilmore, J., Wiedenheft, B., Young, M., and Lawrence, C. M.:
Crystal structure of F-93 from Sulfolobus spindle-shaped virus 1, a winged-helix DNA binding protein.
Journal of Virology (2004) 78, 11544-11550.

Kraft, P., Kummel, D., Oeckinghaus, A., Gauss, G. H., Wiedenheft, B., Young, M., and Lawrence, C. M. :
Structure of D-63 from sulfolobus spindle-shaped virus 1: Surface properties of the dimeric four-helix bundle suggest an adaptor protein function
Journal of Virology (2004) 78, 7438-7442.

Larson, E. T., Reiter, D., Young, M., and Lawrence, C. M. :
Structure of A197 from Sulfolobus turreted icosahedral virus: a crenarchaeal viral glycosyltransferase exhibiting the GT-A fold.
Journal of Virology (2006) 80, 7636-7644.


Structure, Biochemistry

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