NAME: Phil Jeffrey

AFFILIATION: Princeton University, USA

CONTACT: pjeffrey@Princeton.edu

TITLE: "Analysis of Problems with the ABC Transporter Structure Determination"

ABSTRACT:ATP-Binding Cassette (ABC) proteins are the largest family of transmembrane proteins, using ATP to transport a diverse range of molecules across cell membranes. The recent report of the Sev1866 ABC transporter structure by Dawson and Locher (ref. 1) gave rise to the realization that the earlier structures of the ABC transporters MsbA and EmrE (refs. 2-4) had been determined in the incorrect inverted topology (ref. 5).

Inversion of these structures was triggered by an accidental change in sign of the anomalous signal in the experimental diffraction data used for phasing, and compounded by the relatively low resolutions of the structure determinations and refinements (4 Ångstrom or lower). Aspects of the structure determination that caused the original error, and refinement strategies that exacerbated this problem will be discussed and analyzed.

1. R.J. Dawson and K.P. Locher (2006) Nature 443:180-185.
2. G. Chang and C.B. Roth (2001) Science 293:1793-1800.
3. C.L. Reyes and G. Chang (2005) Science 308:1028-1031.
4. O. Pornillos, Y.J. Chen, A.P. Chen and G. Chang (2005) Science 310:1950-1953.
5. G. Chang, C.B. Roth, C.L. Reyes, O. Pornillos, Y.J. Chen and A.P. Chen (2006) Science 314:1875.