James Head, Ph.D.

Research

Structural studies of protein-ligand and protein-protein interactions.

Research in our lab focuses on characterizing the molecular details of protein-ligand and protein-protein interactions and the mechanisms by which changes in these interactions regulate physiological processes. These studies have concentrated mainly on the role of the calcium ion in mediating changes in protein-ligand interactions which subsequently may alter protein-protein interactions to modulate function. However, other protein-ligand interactions are also under study including enzyme-effector and protein-protein complexes. X-ray crystallography is a major tool used in these studies.

Selected Publications:

The crystal structure of the photoprotein aequorin at 2.3A resolution. (2000) Head, J.F. Inouye, S., Teranishi, K. and Shimomura, O. Nature, 405, 372-376.

A crystal structure of the nucleoplasmin-core decamer suggests a model for histone octamer and nucleosome assembly. (2001.) S. Dutta, I.V. Akey, C. Dingwall, K.L. Hartman, T. Laue, R.T. Nolte, J.F. Head, C.W. Akey. Molecular Cell 8: 841-853.

The crystal structure of MarR a regulator of multiple antibiotic resistance at 2.3 Å resolution. (2001) M. N. Alekshun, S. B. Levy, T. R. Mealy, B. A. Seaton and J. F. Head. Nature Structural Biology 8, 710-714.

J.F. Head , N. Swamy, R. Ray Crystal Structure of the Complex between Actin and Human Vitamin D-Binding Protein at 2.5 A Resolution. Biochemistry. (2002) Jul 23;41(29):9015-20.

Head JF, Mealy TR, McCormack FX, Seaton BA (2003) Crystal structure of trimeric carbohydrate recognition and neck domains of surfactant protein A. J. Biol. Chem. 278:43254-43260.

Namboodiri VM, Akey IV, Schmidt-Zachmann MS, Head JF, Akey CW. (2004) The Structure and Function of Xenopus NO38-Core, a Histone Chaperone in the Nucleolus. Structure 12:2149-60.

Meng, J., Vardar, D., Wang, Y., Guo, H-W., Head, J.F. and McKnight, CJ. (2005) The High Resolution Crystal Structures of Villin Headpiece and Mutants with Reduced F-Actin Binding Activity. Biochemistry 44:11963-73.

Crouch, E.C., Smith, K., McDonald, B., Briner, D., Linders, B., McDonald, J., Holmskov, U., Head, J.F., and Hartshorn, K. (2006) Species Differences in the Carbohydrate Binding Preferences of Surfactant Protein D. American Journal of Respiratory Cell and Molecular Biology 35:84-94.

Crouch, E.C., McDonald, B., Smith, K., Cafarella, T., Seaton, B.A., Head, J.F. (2006) Contributions of Phe335 to Carbohydrate Recognition by Human Surfactant Protein D: Stacking Interactions with Lung Collectin Ligands. J. Biol. Chem. 30:18008-14.

Shao C, Zhang F, Kemp MM, Linhardt RJ, Waisman DM, Head JF, Seaton BA. (2006). Crystallographic analysis of calcium-dependent heparin binding to annexin A2. J Biol Chem. 281, 31689-31695.

Shao C, Shi X, Wehbi H, Zambonelli C, Head JF, Seaton BA, Roberts MF. (2007) Dimer structure of an interfacially impaired phosphatidylinositol-specific phospholipase C. J Biol Chem.;282(12):9228-35.

Crouch E, McDonald B, Smith K, Roberts M, Mealy T, Seaton B, Head J. (2007) Critical Role of Arg/Lys343 in the Species-Dependent Recognition of Phosphatidylinositol by Pulmonary Surfactant Protein D. Biochemistry. 46(17):5160-9.

Wang H, Head J, Kosma P, Brade H, Müller-Loennies S, Sheikh S, McDonald B, Smith K, Cafarella T, Seaton B, Crouch E. (2008) Recognition of heptoses and the inner core of bacterial lipopolysaccharides by surfactant protein d. Biochemistry.;47(2):710-20.

Wang L, Brauner JW, Mao G, Crouch E, Seaton B, Head J, Smith K, Flach CR, Mendelsohn R. (2008) Interaction of recombinant surfactant protein D with lipopolysaccharide: conformation and orientation of bound protein by IRRAS and simulations. Biochemistry. 47(31):8103-13.

Shao C, Novakovic VA, Head JF, Seaton BA, Gilbert GE. (2008) Crystal structure of lactadherin C2 domain at 1.7A resolution with mutational and computational analyses of its membrane-binding motif. J Biol Chem.;283(11):7230-41

Shi X, Shao C, Zhang X, Zambonelli C, Redfield AG, Head JF, Seaton BA, Roberts MF (2009). Modulation of Bacillus thuringiensis phosphatidylinositol-specific phospholipase C activity by mutations in the putative dimerization interface. J Biol Chem.284(23):15607-18.

Raychaudhury S, Farelli JD, Montminy TP, Matthews M, Ménétret JF, Duménil G, Roy CR, Head JF, Isberg RR, Akey CW. (2009). Structure and function of interacting IcmR-IcmQ domains from a type IVb secretion system in Legionella pneumophila. Structure. 17(4):590-601.

Crouch E, Hartshorn K, Horlacher T, McDonald B, Smith K, Cafarella T, Seaton B, Seeberger PH, Head J. (2009) Recognition of mannosylated ligands and influenza A virus by human surfactant protein D: contributions of an extended site and residue 343. Biochemistry.48(15):3335-45.

Collaboration

Collaborative efforts are in progress with a number of other research workers within Boston University School of Medicine and elsewhere:

Dr. Christopher Akey, Dept. Physiology and Biophysics, BUSM

Dr. Erika Crouch, Dept Path. & Immunol., Washington University School of Medicine, St. Louis.

Dr. Kevan Hartshorn, Dept Medicine, BU. Medical Center, Boston.

Dr. Satoshi Inouye, Chisso Corp., Yokohama, Japan.

Dr. Stuart Levy, Tufts University School of Medicine. Boston.

Dr. Frank McCormack, Dept. Pulmonary and Critical Care Medicine, Univ. Cincinatti, OH.

Dr. Barbara Seaton, Dept. Physiology and Biophysics, BUSM.

Teaching:

Physiology and Biophysics (dental school) – MD541

Medical Physiology (medical/graduate school) – MED MS134/GMS PH740

Endocrinology – Course manager (medical/graduate school) – MED MS128/GMS PH748

Endocrinology – Course manager (graduate school) – GMS PH750

Advanced Human Physiology A/B (graduate school) – GMS PH 730/731

Experimental Methods in Physiology (graduate school) – GMS PH 741

Cell Biology (graduate school) – CM753

Contact Us

Chobanian & Avedisian School of Medicine
Department of Pharmacology, Physiology and Biophysics

700 Albany Street
Boston MA 02118-2526
Phone:(617) 358-8445
e-mail: head@bu.edu