1roc: Difference between revisions

Revision as of 15:53, 21 February 2008

Crystal structure of the histone deposition protein Asf1

OverviewOverview

BACKGROUND: Asf1 is a ubiquitous eukaryotic histone binding and deposition protein that mediates nucleosome formation in vitro and is required for genome stability in vivo. Studies in a variety of organisms have defined Asf1's role as a histone chaperone during DNA replication through specific interactions with histones H3/H4 and the histone deposition factor CAF-I. In addition to its role in replication, conserved interactions with proteins involved in chromatin silencing, transcription, chromatin remodeling, and DNA repair have also established Asf1 as an important component of a number of chromatin assembly and modulation complexes. RESULTS: We demonstrate that the highly conserved N-terminal domain of S. cerevisiae Asf1 (Asf1N) is the core region that mediates all tested functions of the full-length protein. The crystal structure of this core domain, determined to 1.5 A resolution, reveals a compact immunoglobulin-like beta sandwich fold topped by three helical linkers. The surface of Asf1 displays a conserved hydrophobic groove flanked on one side by an area of strong electronegative surface potential. These regions represent potential binding sites for histones and other interacting proteins. The structural model also allowed us to interpret mutagenesis studies of the human Asf1a/HIRA interaction and to functionally define the region of Asf1 responsible for Hir1-dependent telomeric silencing in budding yeast. CONCLUSIONS: The evolutionarily conserved, N-terminal 155 amino acids of histone deposition protein Asf1 are functional in vitro and in vivo. This core region of Asf1 adopts a compact immunoglobulin-fold structure with distinct surface characteristics, including a Hir protein binding region required for gene silencing.

About this StructureAbout this Structure

1ROC is a Single protein structure of sequence from Saccharomyces cerevisiae with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

Structure and function of the conserved core of histone deposition protein Asf1., Daganzo SM, Erzberger JP, Lam WM, Skordalakes E, Zhang R, Franco AA, Brill SJ, Adams PD, Berger JM, Kaufman PD, Curr Biol. 2003 Dec 16;13(24):2148-58. PMID:14680630

Page seeded by OCA on Thu Feb 21 14:53:04 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1roc.gif|left|200px]]<br /><applet load="1roc" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1roc.gif|left|200px]]<br /><applet load="1roc" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1roc, resolution 1.50&Aring;" />
 '''Crystal structure of the histone deposition protein Asf1'''<br />
 ==Overview==
-BACKGROUND: Asf1 is a ubiquitous eukaryotic histone binding and deposition, protein that mediates nucleosome formation in vitro and is required for, genome stability in vivo. Studies in a variety of organisms have defined, Asf1's role as a histone chaperone during DNA replication through specific, interactions with histones H3/H4 and the histone deposition factor CAF-I., In addition to its role in replication, conserved interactions with, proteins involved in chromatin silencing, transcription, chromatin, remodeling, and DNA repair have also established Asf1 as an important, component of a number of chromatin assembly and modulation complexes., RESULTS: We demonstrate that the highly conserved N-terminal domain of S., cerevisiae Asf1 (Asf1N) is the core region that mediates all tested, functions of the full-length protein. The crystal structure of this core, domain, determined to 1.5 A resolution, reveals a compact, immunoglobulin-like beta sandwich fold topped by three helical linkers., The surface of Asf1 displays a conserved hydrophobic groove flanked on one, side by an area of strong electronegative surface potential. These regions, represent potential binding sites for histones and other interacting, proteins. The structural model also allowed us to interpret mutagenesis, studies of the human Asf1a/HIRA interaction and to functionally define the, region of Asf1 responsible for Hir1-dependent telomeric silencing in, budding yeast. CONCLUSIONS: The evolutionarily conserved, N-terminal 155, amino acids of histone deposition protein Asf1 are functional in vitro and, in vivo. This core region of Asf1 adopts a compact immunoglobulin-fold, structure with distinct surface characteristics, including a Hir protein, binding region required for gene silencing.
+BACKGROUND: Asf1 is a ubiquitous eukaryotic histone binding and deposition protein that mediates nucleosome formation in vitro and is required for genome stability in vivo. Studies in a variety of organisms have defined Asf1's role as a histone chaperone during DNA replication through specific interactions with histones H3/H4 and the histone deposition factor CAF-I. In addition to its role in replication, conserved interactions with proteins involved in chromatin silencing, transcription, chromatin remodeling, and DNA repair have also established Asf1 as an important component of a number of chromatin assembly and modulation complexes. RESULTS: We demonstrate that the highly conserved N-terminal domain of S. cerevisiae Asf1 (Asf1N) is the core region that mediates all tested functions of the full-length protein. The crystal structure of this core domain, determined to 1.5 A resolution, reveals a compact immunoglobulin-like beta sandwich fold topped by three helical linkers. The surface of Asf1 displays a conserved hydrophobic groove flanked on one side by an area of strong electronegative surface potential. These regions represent potential binding sites for histones and other interacting proteins. The structural model also allowed us to interpret mutagenesis studies of the human Asf1a/HIRA interaction and to functionally define the region of Asf1 responsible for Hir1-dependent telomeric silencing in budding yeast. CONCLUSIONS: The evolutionarily conserved, N-terminal 155 amino acids of histone deposition protein Asf1 are functional in vitro and in vivo. This core region of Asf1 adopts a compact immunoglobulin-fold structure with distinct surface characteristics, including a Hir protein binding region required for gene silencing.
 ==About this Structure==
-ROC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with BR as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ROC OCA].
+ROC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=BR:'>BR</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ROC OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Saccharomyces cerevisiae]]
 [[Category: Single protein]]
-[[Category: Adams, P.D.]]
+[[Category: Adams, P D.]]
-[[Category: Berger, J.M.]]
+[[Category: Berger, J M.]]
-[[Category: Brill, S.J.]]
+[[Category: Brill, S J.]]
-[[Category: Daganzo, S.M.]]
+[[Category: Daganzo, S M.]]
-[[Category: Erzberger, J.P.]]
+[[Category: Erzberger, J P.]]
-[[Category: Franco, A.A.]]
+[[Category: Franco, A A.]]
-[[Category: Kaufman, P.D.]]
+[[Category: Kaufman, P D.]]
-[[Category: Lam, W.M.]]
+[[Category: Lam, W M.]]
 [[Category: Skordalakes, E.]]
 [[Category: Zhang, R.]]
@@ Line 26: / Line 26: @@
 [[Category: beta-sandwich]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 01:44:59 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:53:04 2008''