Don M. Engelman

Donald M. Engelman began his science as an undergraduate in Physics, followed by a Ph.D. and postdoctoral work in Biophysics. He took an early interest in membranes, discovering the nature of the membrane lipid phase transition and proving that bilayer structure exists in membranes. Studies of pure lipid systems showed that phases coexist, and ideas of protein structure and folding principles were proposed and tested over years that included key interactions with J-L Popot.

In the course of his folding studies, the pHLIP peptide was discovered: a peptide, derived from Bacteriorhodopsin, that is soluble in water, binds in an unfolded form at membrane surfaces at neutral pH, and folds across the membrane as a helix when the pH is lowered. The properties of the peptide allow new studies of peptide insertion across bilayers. Current work is focused on the uses of pHLIP in targeting tumors, which are acidic, for imaging and drug delivery.



Address:

Department of Molecular Biophysics & Biochemistry, Yale
P.O. Box 208114
New Haven, CT 06520-8114
USA
Lab Web page:http://www.yale.edu/engelman/index.html

Selected Articles:

  1. "X-ray diffraction studies of phase transitions in the membrane of Mycoplasma laidlawii"
Engelman DM,
Journal of Molecular Biology (1970) 47, 115-7
  2. "Bilayer structure in membranes"
Wilkins MH, Blaurock AE and Engelman DM,
Nature New Biol (1971) 230, 72-6.
  3. "The use of x-ray scattering in the study of lipid bilayer planar organization"
 Engelman DM, 
Biophysical Journal (1975) 15, 940-4.
  4. "Path of the polypeptide in bacteriorhodopsin" 
Engelman DM, Henderson R, McLachlan AD and Wallace BA, 
Proc Natl Acad Sci USA (1980) 77, 2023-7.
  5. "Lipid bilayer thickness varies linearly with acyl chain length in fluid phosphatidylcholine vesicles"
Lewis BA and Engelman DM. 
Journal of Molecular Biology (1983) 166, 211-7.
  6. "Refolding of bacteriorhodopsin in lipid bilayers. A thermodynamically controlled two-stage process"
Popot JL, Gerchman SE and Engelman DM. 
Journal of Molecular Biology (1987) 198, 655-76.
  7. "Thermodynamic measurements of the contributions of helix-connecting loops and of retinal to the stability of bacteriorhodopsin"
Kahn TW, Sturtevant JM and Engelman DM.
Biochemistry (1992) 31, 8829-39.
  8. "Sequence specificity in the dimerization of transmembrane alpha-helices"
Lemmon MA, Flanagan JM, Treutlein HR, Zhang J and Engelman DM. 
Biochemistry (1992) 31, 12719-25.
  9. "A transmembrane helix dimer: structure and implications"
MacKenzie KR, Prestegard JH and Engelman DM. 
Science (1997) 276, 131-3.
  10. "Statistical analysis of amino acid patterns in transmembrane helices: the GxxxG motif occurs frequently and in association with beta-branched residues at neighboring positions"
Senes A, Gerstein M and Engelman DM. 
Journal of Molecular Biology (2000) 296,921-36.
  11. "Interhelical hydrogen bonding drives strong interactions in membrane proteins"
Zhou FX, Cocco MJ, Russ WP, Brunger AT and Engelman DM. 
Nature Struct Biol (2000) 7, 154-60.
  12. "Transmembrane protein domains rarely use covalent domain recombination as an evolutionary mechanism"
 Liu Y, Gerstein M and Engelman. DM
Proc Natl Acad Sci USA (2004) 101, 3495-7.
  13. "A monomeric membrane peptide that lives in three worlds: in solution, attached to, and inserted across lipid bilayers"
Reshetnyak YK, Segala M, Andreev OA and Engelman DM. 
Biophysical Journal (2007) 93, 2363-72.
  14. "Measuring Tumor Aggressiveness and Targeting Metastatic Lesions with Fluorescent pHLIP"
Reshetnyak YK, Yao L, Zheng S, Kuznetsov S, Engelman DM, Andreev OA. 
Mol Imaging Biol. 2010 Dec 23.

Selected Reviews:

  1. "Neutron-scattering studies of the ribosome" 
Engelman DM and Moore. PB
Sci Am (1976) 235, 44-54.
  2. "The spontaneous insertion of proteins into and across membranes: the helical hairpin hypothesis"
 Engelman DM and Steitz TA
Cell (1981) 23, 411-22.
  3. "Identifying nonpolar transbilayer helices in amino acid sequences of membrane proteins"
Engelman DM, Steitz TA and Goldman A. 
Annual review of biophysics and biophysical chemistry (1986) 15, 321-53.
  4. "Membrane protein folding and oligomerization: the two-stage model"
Popot JL and Engelman DM.
Biochemistry (1990) 29,4031-7.
  5. "Helical membrane protein folding, stability, and evolution" 
Popot JL and Engelman DM. 
Annu. Rev. Biochem. (2000) 69, 881-922.
  6. "Membrane protein folding: beyond the two stage model"
Engelman DM, Chen Y, Chin CN, Curran AR, Dixon AM, Dupuy AD, Lee AS, Lehnert U, Matthews EE, Reshetnyak YK, Senes A and Popot JL. 
FEBS Letters (2003) 555, 122-5.
  7. "Membranes are more mosaic than fluid"
Engelman DM.
Nature (2005) 438, 578-80.