Dr. Eileen Lafer's lab studies the molecular machines involved in vesicular traffic, a
fundamental process utilized by all compartmentalized cells from yeast
to man to move proteins between different membranous compartments.
initial interest in this subject grew out of our efforts to dissect the
molecular mechanisms underlying synaptic transmission. We showed that
the clathrin pathway is essential for synaptic vesicle recycling. We
went on to characterize the mechanisms of clathrin polymerization and
uncoating that underlie this process. The uncoating reaction is promoted
by the chaperone protein Hsc70, which is a member of the Hsp70 family
of chaperone proteins. These chaperone proteins are also involved in
many aging related disorders that are a consequence of the accumulation
of damaged, aggregated proteins (Alzheimer's, ALS, Parkinson's,
Huntington's, and others). Therefore we are also interested in
understanding the roles these chaperones play in both protein
aggregation diseases and cancer during the aging process. We utilize a
combination of biochemical and physiological approaches including
solution biochemistry (surface plasmon resonance, dynamic light
scattering, analytical ultracentrifugation, nuclear magnetic resonance
spectroscopy), X-ray crystallography, and electrophysiology. Our work
has broad significance since chaperones are involved in many
macromolecular complex remodeling reactions.
A link to my full publication list can be found
Y. Zhuo, K.E. Cano, L. Wang, U. Ilangovan, A.P. Hinck, R.
Sousa and E.M. Lafer. Nuclear Magnetic Resonance Structural Mapping
Reveals Promiscuous Interactions between Clathrin-Box Motif Sequences and the
N-Terminal Domain of the Clathrin Heavy Chain. Biochemistry, 54
2571-2580, 2015. PMCID: PMC4429812.
and E.M. Lafer. The Role Of Molecular Chaperones In Clathrin Mediated Vesicular Trafficking. Frontiers in Molecular Biosciences, 2:26
Morgan JR, Jiang J, Oliphint PA, Jin S, Gimenez LE, Busch DJ, Foldes AE, Zhuo Y, Sousa R, Lafer EM. A role for an Hsp70 nucleotide exchange factor in the regulation of synaptic vesicle endocytosis. J Neurosci. 2013 May 1;33(18):8009-21.
Zhuo Y, Ilangovan U, Schirf V, Demeler B, Sousa R, Hinck AP, Lafer EM. Dynamic interactions between clathrin and locally structured elements in a disordered protein mediate clathrin lattice assembly. J Mol Biol. 2010 Nov 26;404(2):274-90.
Woo HJ, Jiang J, Lafer EM, Sousa R. ATP-induced conformational changes in Hsp70: molecular dynamics and experimental validation of an in silico predicted conformation. Biochemistry. 2009 Dec 8;48(48):11470-7.
Schuermann JP, Jiang J, Cuellar J, Llorca O, Wang L, Gimenez LE, Jin S,
Taylor AB, Demeler B, Morano KA, Hart PJ, Valpuesta JM, Lafer EM, Sousa
R. Structure of the Hsp110:Hsc70 nucleotide exchange machine. Mol Cell. 2008 Jul 25;31(2):232-43.
Jiang J, Maes EG, Taylor AB, Wang L, Hinck AP, Lafer EM, Sousa R. Structural basis of J cochaperone binding and regulation of Hsp70. Mol Cell. 2007 Nov 9;28(3):422-33.