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Published October 28, 2011 | Accepted Version
Journal Article Open

Structure of an Enclosed Dimer Formed by the Drosophila Period Protein

Abstract

Period (PER) is the major transcription inhibitor in metazoan circadian clocks and lies at the center of several feedback loops that regulate gene expression. Dimerization of Drosophila PER influences nuclear translocation, repressor activity, and behavioral rhythms. The structure of a central, 346-residue PER fragment reveals two associated PAS (Per-Arnt-Sim) domains followed by a protruding α-helical extension (αF). A closed, pseudosymmetric dimer forms from a cross handshake interaction of the N-terminal PAS domain with αF of the opposing subunit. Strikingly, a shift of αF against the PAS β-sheet generates two alternative subunit interfaces in the dimer. Taken together with a previously reported PER structure in which αF extends, these data indicate that αF unlatches to switch association of PER with itself to its partner Timeless. The variable positions of the αF helix provide snapshots of a helix dissociation mechanism that has relevance to other PAS protein systems. Conservation of PER interaction residues among a family of PAS-AB-containing transcription factors suggests that contacts mediating closed PAS-AB dimers serve a general function.

Additional Information

© 2011 Elsevier Ltd. Received 4 May 2011; revised 19 August 2011; Accepted 23 August 2011. Edited by R. Huber. Available online 3 September 2011. We thank L. Saez and D. Seay for comments on the manuscript, J. Steiglitz for technical assistance in crystallization, and H. Deng for instruction in use of the SMART system chromatography equipment. Support for H.K. came from the Training Program in Chemical Biology (a joint collaboration among Cornell University, The Rockefeller University, Memorial Sloan-Kettering Cancer Center, and the Weill Medical College of Cornell). A.H. was supported by a Specialized Center of Research grant of the Leukemia and Lymphoma Society and a V Scholar Award from the V Foundation for Cancer Research. This work was also supported by grants from the National Institutes of Health to M.W.Y. (GM054339 and NS053087) and to B.R.C. (GM079679).

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August 22, 2023
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