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排序方式: 共有561条查询结果,搜索用时 31 毫秒
441.
Alessandra Tosco Maria Chiara Monti Bianca Fontanella Sandro Montefusco Luca D’Andrea Barbara Ziaco Daniela Baldantoni Marie-Christine Rio Liberato Marzullo 《Cellular and molecular life sciences : CMLS》2010,67(11):1943-1955
Trefoil protein 1 (TFF1) is a small secreted protein belonging to the trefoil factor family of proteins, that are present
mainly in the gastrointestinal (GI) tract and play pivotal roles as motogenic factors in epithelial restitution, cell motility,
and other incompletely characterized biological processes. We previously reported the up-regulation of TFF1 gene in copper
deficient rats and the unexpected property of the peptide to selectively bind copper. Following the previous evidence, here
we report the characterization of the copper binding site by fluorescence quenching spectroscopy and mass spectrometric analyses.
We demonstrate that Cys58 and at least three Glu surrounding residues surrounding it, are essential to efficiently bind copper.
Moreover, copper binding promotes the TFF1 homodimerization, thus increasing its motogenic activity in in vitro wound healing
assays. Copper levels could then modulate the TFF1 functions in the GI tract, as well as its postulated role in cancer progression
and invasion. 相似文献
442.
Daniela Barretto Barbosa Trivella José Ribamar Ferreira-Júnior Laure Dumoutier Jean-Christophe Renauld Igor Polikarpov 《Cellular and molecular life sciences : CMLS》2010,67(17):2909-2935
The IL-10 family of cytokines is comprised of IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, and IFN-λs (IL-28A, IL-28B, and IL-29).
The IL-10 family members bind to shared class II cytokine receptor chains that associate in various combinations in heterodimeric
complexes. Upon interleukin/receptor complex formation, these proteins switch on the Jak/STAT pathway and elicit pleiotropic
biological responses whose variety sharply contrasts with their structural similarities. IL-10 family members are involved
in several human diseases and health conditions and hence their structural analyses may provide valuable information to design
specific therapeutic strategies. In this review, we describe the human interleukin-10 family of cytokines, focusing on their
structures and functions, with particular attention given to IL-22 and IL-10. We report on the recently published structures
of IL-10 cytokine family members and their complexes with cognate transmembrane and soluble receptors as well as on interleukin
physiology and physiopathology. 相似文献
443.
444.
Chiara F. Valori Liliana Brambilla Francesca Martorana Daniela Rossi 《Cellular and molecular life sciences : CMLS》2014,71(2):287-297
Despite indisputable progress in the molecular and genetic aspects of amyotrophic lateral sclerosis (ALS), a mechanistic comprehension of the neurodegenerative processes typical of this disorder is still missing and no effective cures to halt the progression of this pathology have yet been developed. Therefore, it seems that a substantial improvement of the outcome of ALS treatments may depend on a better understanding of the molecular mechanisms underlying neuronal pathology and survival as well as on the establishment of novel etiological therapeutic strategies. Noteworthy, a convergence of recent data from multiple studies suggests that, in cellular and animal models of ALS, a complex pathological interplay subsists between motor neurons and their non-neuronal neighbours, particularly glial cells. These observations not only have drawn attention to the physiopathological changes glial cells undergo during ALS progression, but they have moved the focus of the investigations from intrinsic defects and weakening of motor neurons to glia–neuron interactions. In this review, we summarize the growing body of evidence supporting the concept that different glial populations are critically involved in the dreadful chain of events leading to motor neuron sufferance and death in various forms of ALS. The outlined observations strongly suggest that glial cells can be the targets for novel therapeutic interventions in ALS. 相似文献
445.
Seyyed Abolghasem Ghadami Francesco Bemporad Benedetta Maria Sala Guido Tiana Stefano Ricagno Fabrizio Chiti 《Cellular and molecular life sciences : CMLS》2017,74(19):3577-3598
Transthyretin (TTR) is an extracellular protein able to deposit into well-defined protein aggregates called amyloid, in pathological conditions known as senile systemic amyloidosis, familial amyloid polyneuropathy, familial amyloid cardiomyopathy and leptomeningeal amyloidosis. At least three distinct partially folded states have been described for TTR, including the widely studied amyloidogenic state at mildly acidic pH. Here, we have used fluorescence resonance energy transfer (FRET) experiments in a monomeric variant of TTR (M-TTR) and in its W41F and W79F mutants, taking advantage of the presence of a unique, solvent-exposed, cysteine residue at position 10, that we have labelled with a coumarin derivative (DACM, acceptor), and of the two natural tryptophan residues at positions 41 and 79 (donors). Trp41 is located in an ideal position as it is one of the residues of β-strand C, whose degree of unfolding is debated. We found that the amyloidogenic state at low pH has the same FRET efficiency as the folded state at neutral pH in both M-TTR and W79F-M-TTR, indicating an unmodified Cys10–Trp41 distance. The partially folded state populated at low denaturant concentrations also has a similar FRET efficiency, but other spectroscopic probes indicate that it is distinct from the amyloidogenic state at acidic pH. By contrast, the off-pathway state accumulating transiently during refolding has a higher FRET efficiency, indicating non-native interactions that reduce the Cys10–Trp41 spatial distance, revealing a third distinct conformational state. Overall, our results clarify a negligible degree of unfolding of β-strand C in the formation of the amyloidogenic state and establish the concept that TTR is a highly plastic protein able to populate at least three distinct conformational states. 相似文献
446.
Nikolas Santamaria Marwa Alhothali Maria Harreguy Alfonso Leonid Breydo Vladimir N. Uversky 《Cellular and molecular life sciences : CMLS》2017,74(7):1297-1318
Five structurally and functionally different proteins, an enzyme superoxide dismutase 1 (SOD1), a TAR-DNA binding protein-43 (TDP-43), an RNA-binding protein FUS, a cofilin-binding protein C9orf72, and polypeptides generated as a result of its intronic hexanucleotide expansions, and to lesser degree actin-binding profilin-1 (PFN1), are considered to be the major drivers of amyotrophic lateral sclerosis. One of the features common to these proteins is the presence of significant levels of intrinsic disorder. The goal of this study is to consider these neurodegeneration-related proteins from the intrinsic disorder perspective. To this end, we employed a broad set of computational tools for intrinsic disorder analysis and conducted intensive literature search to gain information on the structural peculiarities of SOD1, TDP-43, FUS, C9orf72, and PFN1 and their intrinsic disorder predispositions, and the roles of intrinsic disorder in their normal and pathological functions. 相似文献
447.
Åsa Fex Svenningsen Svenja Löring Anna Lahn Sørensen Ha Uyen Buu Huynh Simone Hjæresen Nellie Martin Jesper Bonnet Moeller Maria Louise Elkjær Uffe Holmskov Zsolt Illes Malin Andersson Solveig Beck Nielsen Eirikur Benedikz 《Cellular and molecular life sciences : CMLS》2017,74(24):4561-4572
Macrophage migration inhibitory factor (MIF), a small conserved protein, is abundant in the immune- and central nervous system (CNS). MIF has several receptors and binding partners that can modulate its action on a cellular level. It is upregulated in neurodegenerative diseases and cancer although its function is far from clear. Here, we report the finding of a new binding partner to MIF, the serine protease HTRA1. This enzyme cleaves several growth factors, extracellular matrix molecules and is implicated in some of the same diseases as MIF. We show that the function of the binding between MIF and HTRA1 is to inhibit the proteolytic activity of HTRA1, modulating the availability of molecules that can change cell growth and differentiation. MIF is therefore the first endogenous inhibitor ever found for HTRA1. It was found that both molecules were present in astrocytes and that the functional binding has the ability to modulate astrocytic activities important in development and disease of the CNS. 相似文献
448.
449.
Kiave-Yune HoWangYin Maria Loustau Juan Wu Estibaliz Alegre Marina Daouya Julien Caumartin Sylvie Sousa Anatolij Horuzsko Edgardo D. Carosella Joel LeMaoult 《Cellular and molecular life sciences : CMLS》2012,69(23):4041-4049
The non-classical Human leukocyte antigen G (HLA-G) differs from classical HLA class I molecules by its low genetic diversity, a tissue-restricted expression, the existence of seven isoforms, and immuno-inhibitory functions. Most of the known functions of HLA-G concern the membrane-bound HLA-G1 and soluble HLA-G5 isoforms, which present the typical structure of classical HLA class I molecule: a heavy chain of three globular domains α1–α2–α3 non-covalently bound to β-2-microglobulin (B2M) and a peptide. Very little is known of the structural features and functions of other HLA-G isoforms or structural conformations other than B2M-associated HLA-G1 and HLA-G5. In the present work, we studied the capability of all isoforms to form homomultimers, and investigated whether they could bind to, and function through, the known HLA-G receptors LILRB1 and LILRB2. We report that all HLA-G isoforms may form homodimers, demonstrating for the first time the existence of HLA-G4 dimers. We also report that the HLA-G α1–α3 structure, which constitutes the extracellular part of HLA-G2 and HLA-G6, binds the LILRB2 receptor but not LILRB1. This is the first report of a receptor for a truncated HLA-G isoform. Following up on this finding, we show that the α1–α3-Fc structure coated on agarose beads is tolerogenic and capable of prolonging the survival of skin allografts in B6-mice and in a LILRB2-transgenic mouse model. This study is the first proof of concept that truncated HLA-G isoforms could be used as therapeutic agents. 相似文献
450.
Thomas G Jacobs KB Yeager M Kraft P Wacholder S Orr N Yu K Chatterjee N Welch R Hutchinson A Crenshaw A Cancel-Tassin G Staats BJ Wang Z Gonzalez-Bosquet J Fang J Deng X Berndt SI Calle EE Feigelson HS Thun MJ Rodriguez C Albanes D Virtamo J Weinstein S Schumacher FR Giovannucci E Willett WC Cussenot O Valeri A Andriole GL Crawford ED Tucker M Gerhard DS Fraumeni JF Hoover R Hayes RB Hunter DJ Chanock SJ 《Nature genetics》2008,40(3):310-315