I am seeking a postdoctoral fellow for NMR analysis of the structure of CREB
(cAMP response element binding protein) with its binding site to the
proenkephalin enhancer. Fellow must have experience in multi-dimensional NMR,
and experience in molecular modeling is highly desirable. Interested
candidates should apply by contacting Dr. C. T. McMurray
or by sending a curriculum vitae and three letters of recommendation.
Background of project: The hippocampus is a major excitatory structure,
important for memory and learning. Within the dentate gyrus cells of the
hippocampus, stimulation of glutamate receptors initiates a program of gene
expression that modulates learning. We have found that in the same cell type
initiated by the same receptor, a class of genes that is regulated by identical
transcription factors but have very different rates of transcription. One gene
that is turned on very slowly is the proenkephalin gene. We postulate that the
slow kinetics of transcription is due primarily to a cruciform that forms within
the enhancer (McMurray et al., 1991 PNAS (88) 666). The cruciform is stabilized
by a constitutive protein CREB. CREB bind strongly to one arm of the hairpin.
Strong CREB binding requires at least one mismatched GT base pair that forms
within the stem of the hairpin arm (Spiro et al., 1993 PNAS (90) 4606) and is
also stabilized by loop bases. Electron spectroscopic imaging of the DNA path
within the CREB proenkephalin complex reveals that the DNA assumes an open
state consistent with a cruciform structure (McMurray et al., in preparation).
Project Description: To determine the structure of each arm of the cruciform
that forms from the enhancer, the structure of the a 58 amino acid binding
peptide and the structure of the CREB/enhancer complex.
Contact: Dr. CT McMurray,
Departments of Pharmacology and Biochemistry
Mayo Clinic and Research Foundation,
Rochester, MN 55905.
(507) 284-1597; fax (507) 284-9111.
Collaborators on project:
Dr. Slobodan Macura, NMR director
Dr. Richard Brennan, crystallography of CREB/enk complex.
Institution: The Mayo Clinic is a world renown medical institution that
includes clinic, medical school, graduate school and a research institute. NMR
facility includes a 500MHz multi-nuclear high resolution NMR, a 300MHz widebore
multinuclear NMR with in vivo microimaging accessories, a 4D/320 silicon
graphics workstation, a Personal Iris 4D/35 workstation, analysis program
support from research computing facility.
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Slobodan MACURA INTERNET: macura@mayo.edu
Department of Biochemistry - Gugg. C061Z PHONES: +(507) 284-5917
Mayo Foundation +(507) 284-6937
200 2nd St. SW
Rochester, MN 55905, USA FAX: +(507) 284-8433
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