Abstract:
:The hyaluronate receptor CD44 plays role in cell adhesion and migration and is involved in tumor metastasis. The extracellular domain of CD44 comprises the hyaluronate-binding domain (HABD) and the membrane-proximal stem region; the short intracellular portion interacts with adaptor proteins and triggers signaling pathways. Binding of hyaluronate to CD44 HABD induces an allosteric conformational change, which results in CD44 shedding. A poorly characterized epitope in human CD44 HABD is recognized by the murine monoclonal antibody MEM-85, which cross-blocks hyaluronate binding to CD44 and also induces CD44 shedding. MEM-85 is of therapeutic interest, as it inhibits growth of lung cancer cells in murine models. In this work, we employed a combination of biophysical methods to determine the MEM-85 binding epitope in CD44 HABD and to provide detailed insight into the mechanism of MEM-85 action. In particular, we constructed a single-chain variable fragment (scFv) of MEM-85 as a tool for detailed characterization of the CD44 HABD-antibody complex and identified residues within CD44 HABD involved in the interaction with scFv MEM-85 by NMR spectroscopy and mutational analysis. In addition, we built a rigid body model of the CD44 HABD-scFv MEM-85 complex using a low-resolution structure obtained by small-angle X-ray scattering. The MEM-85 epitope is situated in the C-terminal part of CD44 HABD, rather than the hyaluronate-binding groove, and the binding of MEM-85 induces a structural reorganization similar to that induced by hyaluronate. Therefore, the mechanism of MEM-85 cross-blocking of hyaluronate binding is likely of an allosteric, relay-like nature.
journal_name
J Struct Bioljournal_title
Journal of structural biologyauthors
Škerlová J,Král V,Kachala M,Fábry M,Bumba L,Svergun DI,Tošner Z,Veverka V,Řezáčová Pdoi
10.1016/j.jsb.2015.06.005subject
Has Abstractpub_date
2015-08-01 00:00:00pages
214-23issue
2eissn
1047-8477issn
1095-8657pii
S1047-8477(15)30009-5journal_volume
191pub_type
杂志文章abstract::We have previously used cryo-electron tomography combined with sub-volume averaging and classification to obtain 3D structures of macromolecular assemblies in cases where a single dominant species was present, and applied these methods to the analysis of a variety of trimeric HIV-1 and SIV envelope glycoproteins (Env)...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2012.01.004
更新日期:2012-05-01 00:00:00
abstract::Tricorn protease from the archaeon Thermoplasma acidophilum acts "downstream" of the proteasome; in conjunction with its aminopeptidase cofactors it converts peptides generated by the proteasome into free amino acids. The basic functional unit of Tricorn is a homohexamer of the 121-kDa subunit, 20 of which can assembl...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1006/jsbi.1999.4169
更新日期:1999-12-01 00:00:00
abstract::Accurate knowledge of defocus and tilt parameters is essential for the determination of three-dimensional protein structures at high resolution using electron microscopy. We present two computer programs, CTFFIND3 and CTFTILT, which determine defocus parameters from images of untilted specimens, as well as defocus and...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/s1047-8477(03)00069-8
更新日期:2003-06-01 00:00:00
abstract::The lipopolysaccharide (LPS) of the Salmonella cell surface serves as the receptor for a very large number of bacterial viruses. The tailspike protein from these viruses recognizes the LPS as its initial receptor. It is proposed that the study of the P22 and epsilon 34 tailspike proteins could serve as a model for the...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1006/jsbi.1995.1053
更新日期:1995-11-01 00:00:00
abstract::In Streptomycetes, tetracycline repressor family of transcription regulators (TetR-FTRs) controls various biological processes including antibiotic biosynthesis, cellular morphology and innate resistance. Here, we focus on understanding the structural basis of transcription regulation by CprB, a member of TetR-FTRs fr...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2017.03.006
更新日期:2017-05-01 00:00:00
abstract::The skeletons of demosponges, such as Ianthella basta, are known to be a composite material containing organic constituents. Here, we show that a filigree chitin-based scaffold is an integral component of the I. basta skeleton. These chitin-based scaffolds can be isolated from the sponge skeletons using an isolation a...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2009.06.018
更新日期:2009-12-01 00:00:00
abstract::The mechanisms which cause macromolecules to form discrete compartments within the nucleus are not understood. Here, two ubiquitous compartments, nucleoli, and PML bodies, are shown to disassemble when K562 cell nuclei expand in medium of low monovalent cation concentration; their major proteins dispersed as seen by i...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2003.12.008
更新日期:2004-06-01 00:00:00
abstract::The carboxy-terminal region of the KCNH family of potassium channels contains a cyclic-nucleotide binding homology domain (CNBHD) that is important for channel gating and trafficking. The solution structure of the CNBHD of the KCNH potassium of zebrafish was determined using solution NMR spectroscopy. This domain exis...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2014.03.008
更新日期:2014-04-01 00:00:00
abstract::Virus particle 24 (VP24) is the smallest protein of the Ebola and Marburg virus genomes. Recent experiments show that Ebola VP24 blocks binding of tyrosine-phosphorylated STAT-1 homodimer (PY-STAT1) to the NPI-1 subfamily of importin alpha, thereby preventing nuclear accumulation of this interferon-promoting transcrip...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2009.05.001
更新日期:2009-08-01 00:00:00
abstract::Nacre has long served as a model for understanding the biomineralization mechanism and designing bio-inspired materials. However, its basic building blocks, the aragonite tablets, are still under debate in terms of their fine structure at the nanoscale and corresponding formation mechanism. Here, using a field emissio...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2013.01.010
更新日期:2013-04-01 00:00:00
abstract::Teeth sustain high loads over a lifetime and yet intact tooth failure is rare. The different structures of the tooth, jaw bone and the intervening soft periodontal ligament enable the tooth to endure repeated loading during mastication. Although mechanical and functional properties of the different components are thor...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2011.11.019
更新日期:2012-02-01 00:00:00
abstract::Human coagulation factor VIIai that lacks the Gla domain (residues 1-44) has been prepared, purified, and crystallised. First, recombinant factor VII was activated to form factor VIIa, the active site was then inhibited with 1,5-dansyl-Glu-Gly-Arg-chloromethyl ketone, and finally the Gla domain was removed by chymotry...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1006/jsbi.1998.4078
更新日期:1999-03-01 00:00:00
abstract::3,4-dihydroxy 2-butanone 4-phosphate synthase (DHBPS) and GTP cyclohydrolase-II (GTPCH-II) are the two initial enzymes involved in riboflavin biosynthesis pathway, which has been shown to be essential for the pathogens. In Mycobacterium tuberculosis (Mtb), the ribA2 gene (Rv1415) encodes for the bi-functional enzyme w...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2011.01.013
更新日期:2011-05-01 00:00:00
abstract::The purified glucocorticoid receptor (GR) from rat liver has been visualised by electron microscopy. The specimens were prepared by spreading on thin carbon support and negatively stained using uranyl acetate. Two forms of GR, the monomeric and the dimeric forms, were identified based on size, chromatographic distribu...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/1047-8477(91)90030-z
更新日期:1991-08-01 00:00:00
abstract::Human alpha 2-macroglobulin (alpha 2M), a large tetrameric plasma glycoprotein, inhibits a wide spectrum of proteinases by a particular "trapping" mechanism resulting from the proteolysis of peptide bonds at specific "bait" regions. This induces the hydrolysis of four thiol esters triggering both the possible covalent...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/1047-8477(91)90060-a
更新日期:1991-02-01 00:00:00
abstract::Recent studies reveal that mitochondria take substantial responsibility in cellular functions that are closely related to aging diseases caused by degeneration of neurons. These studies emphasize that the membrane and crista morphology of a mitochondrion should receive attention in order to investigate the link betwee...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2016.03.002
更新日期:2016-06-01 00:00:00
abstract::In order to understand further the mechanism of bone fracture repair, and thus to innovate better operative treatment for bone fracture and to design new implant materials for bone repair, microstructures of external periosteal callus (EPC) of repaired femoral fracture in both children and adults were investigated by ...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1006/jsbi.1996.0084
更新日期:1996-11-01 00:00:00
abstract::The Membrane Attack Complex-Perforin (MACPF) family is ubiquitously found in all kingdoms. They have diverse cellular roles, however MACPFs with pore-forming toxic function in venoms and poisons are very rare in animals. Here we present the structure of PmPV2, a MACPF toxin from the poisonous apple snail eggs, that ca...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2020.107531
更新日期:2020-08-01 00:00:00
abstract::Three-dimensional reconstruction of large macromolecules like viruses at resolutions below 10 A requires a large set of projection images. Several automatic and semi-automatic particle detection algorithms have been developed along the years. Here we present a general technique designed to automatically identify the p...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2003.11.028
更新日期:2004-01-01 00:00:00
abstract::We demonstrate in this work that scanning tunneling microscopy (STM) provides a useful approach to obtaining structural information about human islet amyloid polypeptide (hIAPP) and rat islet amyloid polypeptide (rIAPP) assembly on highly oriented pyrolytic graphite (HOPG) with sub-molecular resolution. The observed h...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2009.05.009
更新日期:2009-09-01 00:00:00
abstract::Processing of nuclear pre-mRNA is an important step in the regulation of gene expression and involves 5(')- and 3(')-end processing, splicing, and editing. Mammalian nuclear pre-mRNAs are assembled in large ribonucleoprotein (lnRNP) complexes, in which the entire population of nuclear pre-mRNA is individually packaged...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/s1047-8477(02)00541-5
更新日期:2002-10-01 00:00:00
abstract::Rlf is a guanine nucleotide exchange factor for the small G-proteins RalA and RalB and couples Ras- to Ral-signalling. Here the crystal structure of the catalytic module of Rlf consisting of a REM- and a CDC25-homology domain is determined. The structure is distinguished by an extended three stranded β-sheet called th...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2013.07.009
更新日期:2013-09-01 00:00:00
abstract::We report here on the current state of our efforts in automated molecular microscopy. Our primary automated data acquisition software system, Leginon, has been completely redesigned over the past two years. The new distributed system has been developed using the Python programming language and is compatible with both ...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2005.03.010
更新日期:2005-07-01 00:00:00
abstract::Riboflavin synthase is a trimer of identical 23-kDa subunits. The primary structure is characterized by considerable similarity of the C-terminal and N-terminal parts. Recombinant riboflavin synthase of Escherichia coli and Bacillus subtilis was crystallized by the vapor diffusion method. Crystals of E. coli riboflavi...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1006/jsbi.1997.3935
更新日期:1998-01-01 00:00:00
abstract::HIV-1 Rev mediates the nuclear export of unspliced and partially-spliced viral transcripts for the production of progeny genomes and structural proteins. In this process, four (or more) copies of Rev assemble onto a highly-structured 351-nt region in such viral transcripts, the Rev response element (RRE). How this occ...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2018.03.011
更新日期:2018-08-01 00:00:00
abstract::The structure of R-phycoerythrin (R-PE) from the red alga Griffithsia monilis was solved at 1.90-A resolution by molecular replacement, using the atomic coordinates of cyanobacterial phycocyanin from Fremyella diplosiphon as a model. The crystallographic R factor for the final model is 17.5% (Rfree 22.7%) for reflecti...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1006/jsbi.1999.4106
更新日期:1999-06-15 00:00:00
abstract::Lipocalin-type prostaglandin D synthase (L-PGDS) acts as both a PGD(2) synthase and an extracellular transporter for small lipophilic molecules. From a series of biochemical studies, it has been found that L-PGDS has an ability to bind a variety of lipophilic ligands such as biliverdin, bilirubin and retinoids in vitr...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2009.10.005
更新日期:2010-02-01 00:00:00
abstract::The QVIEW image-processing software package provides a graphical user interface for interactive and rapid selection of particles from digital electron micrographs. This package was developed to facilitate the selection of elliptical, hydrophobic, and aggregating particles, which present complications for other particl...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1006/jsbi.1998.4011
更新日期:1998-09-01 00:00:00
abstract::Staphylococcus aureus hibernation promoting factor (SaHPF) is responsible for the formation of 100S ribosome dimers, which in turn help this pathogen to reduce energy spent under unfavorable conditions. Ribosome dimer formation strongly depends on the dimerization of the C-terminal domain of SaHPF (CTDSaHPF). In this ...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2019.107408
更新日期:2020-01-01 00:00:00
abstract::Non-collagenous proteins such as osteocalcin function as regulators of the mineralization process in bone. Osteocalcin undergoes post-translational modification adding an extra carboxylate group on three of its glutamate residues to enhance interaction with bone mineral. In this work, we examine regulation of biomimet...
journal_title:Journal of structural biology
pub_type: 杂志文章
doi:10.1016/j.jsb.2019.04.014
更新日期:2019-08-01 00:00:00