The structure of nucleosome assembly protein 1

doi:10.1073/pnas.0508002103

The structure of nucleosome assembly protein 1

Young-Jun Park and
Karolin Luger†

Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523-1870

Edited by Roger D. Kornberg, Stanford University School of Medicine, Stanford, CA, and approved November 29, 2005 (received for review September 14, 2005)

Abstract

Nucleosome assembly protein 1 (NAP-1) is an integral component in the establishment, maintenance, and dynamics of eukaryotic chromatin. It shuttles histones into the nucleus, assembles nucleosomes, and promotes chromatin fluidity, thereby affecting the transcription of many genes. The 3.0 Å crystal structure of yeast NAP-1 reveals a previously uncharacterized fold with implications for histone binding and shuttling. A long α-helix is responsible for homodimerization via a previously uncharacterized antiparallel non-coiled-coil, and an α/β domain is implicated in protein–protein interaction. A nuclear export sequence that is embedded in the dimerization helix is almost completely masked by an accessory domain that contains several target sites for casein kinase II. The four-stranded antiparallel β-sheet that characterizes the α/β domain is found in all histone chaperones, despite the absence of homology in sequence, structural context, or quaternary structure. To our knowledge, this is the first structure of a member of the large NAP family of proteins and suggests a mechanism by which the shuttling of histones to and from the nucleus is regulated.

Footnotes

↵ † To whom correspondence should be addressed. E-mail: karolin.luger{at}colostate.edu.
Author contributions: Y.-J.P. and K.L. performed research.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: NES, nuclear export sequence; NLS, nuclear localization sequence.
Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB ID code 2AYU).
Freely available online through the PNAS open access option.