scholarly journals Crystal structure of the Cenp-HIKHead-TW sub-module of the inner kinetochore CCAN complex

2020 ◽  
Vol 48 (19) ◽  
pp. 11172-11184 ◽  
Author(s):  
Ziguo Zhang ◽  
Dom Bellini ◽  
David Barford
Keyword(s):  
Crystal Structure ◽  
Binding Motif ◽  
Centromeric Chromatin ◽  
Helical Bundle ◽  
Histone Fold ◽  
Chromatid Segregation ◽  
Histone Fold Domain ◽  
Repeat Domain ◽  
Α Helix ◽  
A Site

Abstract Kinetochores are large multi-subunit complexes that attach centromeric chromatin to microtubules of the mitotic spindle, enabling sister chromatid segregation in mitosis. The inner kinetochore constitutive centromere associated network (CCAN) complex assembles onto the centromere-specific Cenp-A nucleosome (Cenp-ANuc), thereby coupling the centromere to the microtubule-binding outer kinetochore. CCAN is a conserved 14–16 subunit complex composed of discrete modules. Here, we determined the crystal structure of the Saccharomyces cerevisiae Cenp-HIKHead-TW sub-module, revealing how Cenp-HIK and Cenp-TW interact at the conserved Cenp-HIKHead–Cenp-TW interface. A major interface is formed by the C-terminal anti-parallel α-helices of the histone fold extension (HFE) of the Cenp-T histone fold domain (HFD) combining with α-helix H3 of Cenp-K to create a compact three α-helical bundle. We fitted the Cenp-HIKHead-TW sub-module to the previously determined cryo-EM map of the S. cerevisiae CCAN–Cenp-ANuc complex. This showed that the HEAT repeat domain of Cenp-IHead and C-terminal HFD of Cenp-T of the Cenp-HIKHead-TW sub-module interact with the nucleosome DNA gyre at a site close to the Cenp-ANuc dyad axis. Our structure provides a framework for understanding how Cenp-T links centromeric Cenp-ANuc to the outer kinetochore through its HFD and N-terminal Ndc80-binding motif, respectively.

Crystal structure of human chondroadherin: solving a difficult molecular-replacement problem usingde novomodels

2017 ◽  
Vol 73 (1) ◽  
pp. 53-63 ◽  
Author(s):  
Sebastian Rämisch ◽  
Anna Pramhed ◽  
Viveka Tillgren ◽  
Anders Aspberg ◽  
Derek T. Logan
Keyword(s):  
Crystal Structure ◽  
Matrix Protein ◽  
De Novo ◽  
Therapeutic Potential ◽  
Protein Structure Determination ◽  
Binding Motif ◽  
Molecular Replacement ◽  
Docking Simulations ◽  
Integrin Binding Site ◽  
Α Helix

Chondroadherin (CHAD) is a cartilage matrix protein that mediates the adhesion of isolated chondrocytes. Its protein core is composed of 11 leucine-rich repeats (LRR) flanked by cysteine-rich domains. CHAD makes important interactions with collagen as well as with cell-surface heparin sulfate proteoglycans and α2β1integrins. The integrin-binding site is located in a region of hitherto unknown structure at the C-terminal end of CHAD. Peptides based on the C-terminal human CHAD (hCHAD) sequence have shown therapeutic potential for treating osteoporosis. This article describes a still-unconventional structure solution by phasing withde novomodels, the first of a β-rich protein. Structure determination of hCHAD using traditional, though nonsystematic, molecular replacement was unsuccessful in the hands of the authors, possibly owing to a combination of low sequence identity to other LRR proteins, four copies in the asymmetric unit and weak translational pseudosymmetry. However, it was possible to solve the structure by generating a large number ofde novomodels for the central LRR domain usingRosettaand multiple parallel molecular-replacement attempts usingAMPLE. The hCHAD structure reveals an ordered C-terminal domain belonging to the LRRCT fold, with the integrin-binding motif (WLEAK) being part of a regular α-helix, and suggests ways in which experimental therapeutic peptides can be improved. The crystal structure itself and docking simulations further support that hCHAD dimers form in a similar manner to other matrix LRR proteins.

scholarly journals The H4 Tail Domain Participates in Intra- and Internucleosome Interactions with Protein and DNA during Folding and Oligomerization of Nucleosome Arrays

2008 ◽  
Vol 29 (2) ◽  
pp. 538-546 ◽  
Author(s):  
Pu-Yeh Kan ◽  
Tamara L. Caterino ◽  
Jeffrey J. Hayes
Keyword(s):  
Tail Domain ◽  
Predominant Role ◽  
Linker Histones ◽  
Histone Fold ◽  
Histone Fold Domain ◽  
Strong Stimulation ◽  
Self Association ◽  
Core Histone Tail ◽  
A Site ◽  
Nucleosome Arrays

ABSTRACT The condensation of nucleosome arrays into higher-order secondary and tertiary chromatin structures likely involves long-range internucleosomal interactions mediated by the core histone tail domains. We have characterized interarray interactions mediated by the H4 tail domain, known to play a predominant role in the formation of such structures. We find that the N-terminal end of the H4 tail mediates interarray contacts with DNA during self-association of oligonucleosome arrays similar to that found previously for the H3 tail domain. However, a site near the histone fold domain of H4 participates in a distinct set of interactions, contacting both DNA and H2A in condensed structures. Moreover, we also find that H4-H2A interactions occur via an intra- as well as an internucleosomal fashion, supporting an additional intranucleosomal function for the tail. Interestingly, acetylation of the H4 tail has little effect on interarray interactions by itself but overrides the strong stimulation of interarray interactions induced by linker histones. Our results indicate that the H4 tail facilitates secondary and tertiary chromatin structure formation via a complex array of potentially exclusive interactions that are distinct from those of the H3 tail domain.

scholarly journals Human CENP-A contains a histone H3 related histone fold domain that is required for targeting to the centromere.

1994 ◽  
Vol 127 (3) ◽  
pp. 581-592 ◽  
Author(s):  
K F Sullivan ◽  
M Hechenberger ◽  
K Masri
Keyword(s):  
Amino Acid ◽  
Molecular Basis ◽  
Core Protein ◽  
Histone H3 ◽  
Animal Cells ◽  
Centromeric Chromatin ◽  
Histone Fold ◽  
Terminal Domain ◽  
Histone Fold Domain ◽  
Mitotic Behavior

Centromeres are the differentiated chromosomal domains that specify the mitotic behavior of chromosomes. To examine the molecular basis for the specification of centromeric chromatin, we have cloned a human cDNA that encodes the 17-kD histone-like centromere antigen, CENP-A. Two domains are evident in the 140 aa CENP-A polypeptide: a unique NH2-terminal domain and a 93-amino acid COOH-terminal domain that shares 62% identity with nucleosomal core protein, histone H3. An epitope tagged derivative of CENP-A was faithfully targeted to centromeres when expressed in a variety of animal cells and this targeting activity was shown to reside in the histone-like COOH-terminal domain of CENP-A. These data clearly indicate that the assembly of centromeres is driven, at least in part, by the incorporation of a novel core histone into centromeric chromatin.

scholarly journals Crystal structures of Ca2+–calmodulin bound to NaV C-terminal regions suggest role for EF-hand domain in binding and inactivation

2019 ◽  
Vol 116 (22) ◽  
pp. 10763-10772 ◽  
Author(s):  
Bernd R. Gardill ◽  
Ricardo E. Rivera-Acevedo ◽  
Ching-Chieh Tung ◽  
Filip Van Petegem
Keyword(s):  
Crystal Structure ◽  
Binding Sites ◽  
Binding Mode ◽  
Conformational Switch ◽  
Channel Inactivation ◽  
Dependent Inactivation ◽  
Ef Hand ◽  
Inherited Arrhythmia ◽  
A Site

Voltage-gated sodium (NaV) and calcium channels (CaV) form targets for calmodulin (CaM), which affects channel inactivation properties. A major interaction site for CaM resides in the C-terminal (CT) region, consisting of an IQ domain downstream of an EF-hand domain. We present a crystal structure of fully Ca2+-occupied CaM, bound to the CT of NaV1.5. The structure shows that the C-terminal lobe binds to a site ∼90° rotated relative to a previous site reported for an apoCaM complex with the NaV1.5 CT and for ternary complexes containing fibroblast growth factor homologous factors (FHF). We show that the binding of FHFs forces the EF-hand domain in a conformation that does not allow binding of the Ca2+-occupied C-lobe of CaM. These observations highlight the central role of the EF-hand domain in modulating the binding mode of CaM. The binding sites for Ca2+-free and Ca2+-occupied CaM contain targets for mutations linked to long-QT syndrome, a type of inherited arrhythmia. The related NaV1.4 channel has been shown to undergo Ca2+-dependent inactivation (CDI) akin to CaVs. We present a crystal structure of Ca2+/CaM bound to the NaV1.4 IQ domain, which shows a binding mode that would clash with the EF-hand domain. We postulate the relative reorientation of the EF-hand domain and the IQ domain as a possible conformational switch that underlies CDI.

scholarly journals Crystal Structure Refinements of Four Monazite Samples from Different Localities

Minerals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1028 ◽  
Author(s):  
M. Mashrur Zaman ◽  
Sytle M. Antao
Keyword(s):  
Crystal Structure ◽  
Electron Probe ◽  
Unit Cell Volume ◽  
Unit Cell ◽  
X Ray Diffraction ◽  
Unit Cell Parameters ◽  
X Ray ◽  
Cell Parameters ◽  
Large Unit Cell ◽  
A Site

This study investigates the crystal chemistry of monazite (APO4, where A = Lanthanides = Ln, as well as Y, Th, U, Ca, and Pb) based on four samples from different localities using single-crystal X-ray diffraction and electron-probe microanalysis. The crystal structure of all four samples are well refined, as indicated by their refinement statistics. Relatively large unit-cell parameters (a = 6.7640(5), b = 6.9850(4), c = 6.4500(3) Å, β = 103.584(2)°, and V = 296.22(3) Å3) are obtained for a detrital monazite-Ce from Cox’s Bazar, Bangladesh. Sm-rich monazite from Gunnison County, Colorado, USA, has smaller unit-cell parameters (a = 6.7010(4), b = 6.9080(4), c = 6.4300(4) Å, β = 103.817(3)°, and V = 289.04(3) Å3). The a, b, and c unit-cell parameters vary linearly with the unit-cell volume, V. The change in the a parameter is large (0.2 Å) and is related to the type of cations occupying the A site. The average <A-O> distances vary linearly with V, whereas the average <P-O> distances are nearly constant because the PO4 group is a rigid tetrahedron.

scholarly journals Mapping and Functional Characterization of the TAF11 Interaction with TFIIA

2005 ◽  
Vol 25 (3) ◽  
pp. 945-957 ◽  
Author(s):  
M. M. Robinson ◽  
G. Yatherajam ◽  
R. T. Ranallo ◽  
A. Bric ◽  
M. R. Paule ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Regulation Of Gene Expression ◽  
Small Subunit ◽  
Molecular Organization ◽  
Functional Link ◽  
Essential Information ◽  
Histone Fold ◽  
Histone Fold Domain ◽  
Promoter Dna

ABSTRACT TFIIA interacts with TFIID via association with TATA binding protein (TBP) and TBP-associated factor 11 (TAF11). We previously identified a mutation in the small subunit of TFIIA (toa2-I27K) that is defective for interaction with TAF11. To further explore the functional link between TFIIA and TAF11, the toa2-I27K allele was utilized in a genetic screen to isolate compensatory mutants in TAF11. Analysis of these compensatory mutants revealed that the interaction between TAF11 and TFIIA involves two distinct regions of TAF11: the highly conserved histone fold domain and the N-terminal region. Cells expressing a TAF11 allele defective for interaction with TFIIA exhibit conditional growth phenotypes and defects in transcription. Moreover, TAF11 imparts changes to both TFIIA-DNA and TBP-DNA contacts in the context of promoter DNA. These alterations appear to enhance the formation and stabilization of the TFIIA-TBP-DNA complex. Taken together, these studies provide essential information regarding the molecular organization of the TAF11-TFIIA interaction and define a mechanistic role for this association in the regulation of gene expression in vivo.

scholarly journals Crystal Structure of an Aquabirnavirus Particle: Insights into Antigenic Diversity and Virulence Determinism

2009 ◽  
Vol 84 (4) ◽  
pp. 1792-1799 ◽  
Author(s):  
Fasséli Coulibaly ◽  
Christophe Chevalier ◽  
Bernard Delmas ◽  
Félix A. Rey
Keyword(s):  
Crystal Structure ◽  
Three Dimensional ◽  
Salient Feature ◽  
Infectious Pancreatic Necrosis Virus ◽  
Antigenic Determinants ◽  
Binding Motif ◽  
Icosahedral Symmetry ◽  
Fold Axis ◽  
Cell Internalization ◽  
Pancreatic Necrosis Virus

ABSTRACT Infectious pancreatic necrosis virus (IPNV), a pathogen of salmon and trout, imposes a severe toll on the aquaculture and sea farming industries. IPNV belongs to the Aquabirnavirus genus in the Birnaviridae family of bisegmented double-stranded RNA viruses. The virions are nonenveloped with a T=13l icosahedral capsid made by the coat protein VP2, the three-dimensional (3D) organization of which is known in detail for the family prototype, the infectious bursal disease virus (IBDV) of poultry. A salient feature of the birnavirus architecture is the presence of 260 trimeric spikes formed by VP2, projecting radially from the capsid. The spikes carry the principal antigenic sites as well as virulence and cell adaptation determinants. We report here the 3.4-Å resolution crystal structure of a subviral particle (SVP) of IPNV, containing 20 VP2 trimers organized with icosahedral symmetry. We show that, as expected, the SVPs have a very similar organization to the IBDV counterparts, with VP2 exhibiting the same overall 3D fold. However, the spikes are significantly different, displaying a more compact organization with tighter packing about the molecular 3-fold axis. Amino acids controlling virulence and cell culture adaptation cluster differently at the top of the spike, i.e., in a central bowl in IBDV and at the periphery in IPNV. In contrast, the spike base features an exposed groove, conserved across birnavirus genera, which contains an integrin-binding motif. Thus, in addition to revealing the viral antigenic determinants, the structure suggests that birnaviruses interact with different receptors for attachment and for cell internalization during entry.

Structural insights into the novel ARM-repeat protein CTNNBL1 and its association with the hPrp19–CDC5L complex

2014 ◽  
Vol 70 (3) ◽  
pp. 780-788 ◽  
Author(s):  
Jae-Woo Ahn ◽  
Sangwoo Kim ◽  
Eun-Jung Kim ◽  
Yeo-Jin Kim ◽  
Kyung-Jin Kim
Keyword(s):  
Crystal Structure ◽  
The Novel ◽  
Molecular Architecture ◽  
Repeat Protein ◽  
Binding Partner ◽  
Catalytic Activation ◽  
Repeat Structure ◽  
Repeat Domain ◽  
Importin Α ◽  
Structural Insights

The hPrp19–CDC5L complex plays a crucial role during human pre-mRNA splicing by catalytic activation of the spliceosome. In order to elucidate the molecular architecture of the hPrp19–CDC5L complex, the crystal structure of CTNNBL1, one of the major components of this complex, was determined. Unlike canonical ARM-repeat proteins such as β-catenin and importin-α, CTNNBL1 was found to contain a twisted and extended ARM-repeat structure at the C-terminal domain and, more importantly, the protein formed a stable dimer. A highly negatively charged patch formed in the N-terminal ARM-repeat domain of CTNNBL1 provides a binding site for CDC5L, a binding partner of the protein in the hPrp19–CDC5L complex, and these two proteins form a complex with a stoichiometry of 2:2. These findings not only present the crystal structure of a novel ARM-repeat protein, CTNNBL1, but also provide insights into the detailed molecular architecture of the hPrp19–CDC5L complex.

scholarly journals β-Li0.37Na0.63Fe(MoO4)2

2014 ◽  
Vol 70 (2) ◽  
pp. i9-i10 ◽  
Author(s):  
Amira Souilem ◽  
Mohamed Faouzi Zid ◽  
Ahmed Driss
Keyword(s):  
Crystal Structure ◽  
Solid State ◽  
Solid State Reaction ◽  
Title Compound ◽  
General Position ◽  
Site Occupancy ◽  
The Other ◽  
Main Structure ◽  
Axis Direction ◽  
A Site

The title compound, lithium/sodium iron(III) bis[orthomolybdate(VI)], was obtained by a solid-state reaction. The main structure units are an FeO6octahedron, a distorted MoO6octahedron and an MoO4tetrahedron sharing corners. The crystal structure is composed of infinite double MoFeO11chains along theb-axis direction linked by corner-sharing to MoO4tetrahedra so as to form Fe2Mo3O19ribbons. The cohesion between ribbonsviamixed Mo—O—Fe bridges leads to layers arranged parallel to thebcplane. Adjacent layers are linked by corners shared between MoO4tetrahedra of one layer and FeO6octahedra of the other layer. The Na+and Li+ions partially occupy the same general position, with a site-occupancy ratio of 0.631 (9):0.369 (1). A comparison is made withAFe(MoO4)2(A= Li, Na, K and Cs) structures.

Sign in / Sign up

Export Citation Format

Share Document