2stt

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2stt

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SOLUTION NMR STRUCTURE OF THE HUMAN ETS1/DNA COMPLEX, 25 STRUCTURES

Overview

The ETS family of transcription factors consists of a group of proteins, that share a highly conserved 85 amino acid DNA-binding domain (DBD). This, family recognizes a consensus sequence rich in purine bases with a central, GGAA motif. A comparison of the published three-dimensional structures of, the DBD/DNA complexes of ETS1 by NMR [Werner et al. (1995) Cell, 83, 761-771] and the related Pu.1 by X-ray crystallography [Kodandapani et al., (1996) Nature, 380, 456-460] reveals an apparent discrepancy in which the, protein domains bind with opposite polarity to their target sequences., This surprising and highly unlikely result prompted us to reexamine our, NMR structure. Additional NMR experiments now reveal an error in the, original interpretation of the spectra defining the orientation of the, ETS1-DBD on DNA. It was originally reported that the ETS1-DBD bound to DNA, with a bipartite motif involving major groove recognition via a, helix-turn-helix element and minor groove recognition via protein, side-chain intercalation. The presence of intercalation was deduced on the, basis of numerous NOEs between several amino acids in the protein and a, resonance at 12.33 ppm originally assigned to a DNA imino proton. New NMR, experiments now conclusively demonstrate that this resonance, which is, located within the DNA imino proton region of the spectrum, arises from, the hydroxyl proton of Tyr86. Realization of this error necessitated, reanalysis of the intermolecular NOEs. This revealed that the orientation, of the ETS1-DBD in the complex is opposite to that originally reported and, that a tryptophan residue does not intercalate into the DNA. The, calculation of a new ensemble of structures based on the corrected data, indicates that the structure of the ETS1-DBD/DNA complex is indeed similar, to the X-ray structure of the Pu.1-DBD/DNA complex.

About this Structure

2STT is a Single protein structure of sequence from Homo sapiens. This structure superseeds the now removed PDB entry 1STT. Full crystallographic information is available from OCA.

Reference

Correction of the NMR structure of the ETS1/DNA complex., Werner MH, Clore GM, Fisher CL, Fisher RJ, Trinh L, Shiloach J, Gronenborn AM, J Biomol NMR. 1997 Dec;10(4):317-28. PMID:9460239

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