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Steven Smith, Ph.D.
Professor of Biochemistry and Director of the
Interdisciplinary Program in Structural Biology.
Funding through the National Institute of General Medical Sciences.
Figure 1. Structural model of CCR5,
one of the two co-receptors in T-cells which allow HIV entry
and infection. An under-graduate, Ted Shieh, using known structural
constraints derived from other G protein coupled receptors,
developed the structural model. The residues in the extracellular
side of the receptor (top-left) have been found experimentally
to form the binding site to a specific inhibitor which prevents
HIV entry. |
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The overall goal of our research has been to understand in structural
and chemical terms how membrane proteins function. Current work focuses
on the molecular mechanisms of signal transduction by G protein-coupled
receptors and receptor tyrosine kinases, and the mechanism of selectivity
and gating by ion channel proteins. Our research on signal transduction
mechanisms mediated by protein conformational changes has involved the
visual pigment rhodopsin, a seven transmembrane helix receptor in vertebrate
rod cells responsible for vision in dim light. More recently, we have
been investigating specific inhibitors to CCR5, a G protein coupled receptor
in T-cells which serves as one of the co-receptors for HIV entry and infection
(Figure 1). Modeling of these receptors based on structural and molecular
biological data is one active area of student research.
Current projects involving signal transduction mediated by receptor oligomerization
focus on two receptor proteins -- the neu or erbB-2 receptor and the platelet-derived
growth factor (PDGF) receptor -- that can be constitutively activated
through interactions involving their transmembrane domains. Student research
projects will involve the use of computational search algorithms to establish
low energy conformations of interacting transmembrane helices. In the
neu receptor, a single mutation in the transmembrane domain leads to receptor
activation and is associated with a large fraction of breast and ovarian
cancers. Finally, structure-function studies are in progress on phospholamban,
a 52-residue ion channel protein found in cardiac sarcoplasmic reticulum
(SR) that regulates calcium levels across the SR membrane. The protein
shares many features with the much larger mammalian ion channels, which
may allow us to investigate how these proteins are regulated in terms
of ion specificity and gating. Students with strong mathematics, physics
and engineering backgrounds can work on complex biological problems using
the tools available in structural and computational biology. State-of-the-art
instrumentation in nuclear magnetic resonance spectroscopy and x-ray crystallography
is available in the new Center for Structure Biology at SUNY Stony Brook.
Student Background: Our research program bridges biology, chemistry and
physics. The ideal student would have a background in chemistry, physics
or mathematics, but with some exposure to and a lot of interest in biology.
Contact Information
email: steven.o.smith@sunysb.edu
url: http://sos.bio.sunysb.edu/
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