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1.
Lactoferrin 总被引:4,自引:0,他引:4
The first function attributed to lactoferrin (Lf), an iron binding protein belonging to the non-immune natural defences, was antimicrobial activity that depended on its capacity to sequester iron. Iron-independent microbicidal activities, requiring direct interaction between this cationic protein and microbial surface components, were later demonstrated. Many other anti-microbial and anti-viral functions have since been ascribed to Lf. In mucosal secretions, iron and Lf modulate the motility and aggregation of pathogenic bacteria. Lf inhibits bacterial adhesion on abiotic surfaces through ionic binding to biomaterials, or specific binding to bacterial structures or both. Lf inhibition of bacterial adhesion to host cells requires Lf binding to bacteria and/or host cells. Lf hinders microbial internalization by binding to both glycosaminoglycans and bacterial proteins which can be degraded by Lf-mediated proteolysis. Moreover, Lf internalisation and localisation to the host cell nuclei could modulate bacterial entry into cells through gene regulation. Finally, the capability of Lf to exert antiviral activity, through its binding to host cells and/or viral particles, strengthens the idea that it is an important brick in the mucosal wall, effective against both microbial and viral attacks. 相似文献
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Mammalian lactoferrin (Lf) receptors are suggested to have pivotal roles for mediating multiple functions of Lf. In this review, we focus on current knowledge of the structure and function of mammalian Lf receptors, mainly the first cloned Lf receptor that has been shown to be expressed in the infant small intestine at high levels but also in virtually all other tissues. The small intestinal Lf receptor takes up iron from Lf into cells and presumably exerts other physiological functions. Other Lf receptors in various tissues have also been reported to mediate some functions of Lf, such as modulating immune function, inhibiting platelet aggregation and enhancing collagen gel contractile strength. The detailed mechanisms behind the receptor-Lf interactions still need to be elucidated. 相似文献
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Ca2+/Calmodulin-dependent Protein Kinases 总被引:1,自引:0,他引:1
In this article the calcium/calmodulin-dependent protein kinases are reviewed. The primary focus is on the structure and function of this diverse family of enzymes, and the elegant regulation of their activity. Structures are compared in order to highlight the conserved architecture of their catalytic domains with respect to each other as well as protein kinase A, a prototype for kinase structure. In addition to reviewing structure and function in these enzymes, the variety of biological processes for which they play a mediating role are also examined. Finally, how the enzymes become activated in the intracellular setting is considered by exploring the reciprocal interactions that exist between calcium binding to calmodulin when interacting with the CaM-kinases. 相似文献
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Protein C inhibitor (PCI) is a widely distributed, multifunctional member of the serpin family of protease inhibitors, and
has been implicated in several physiological processes and disease states. Its inhibitory activity and specificity are regulated
by binding to cofactors such as heparin, thrombomodulin and phospholipids, and it also appears to have non-inhibitory functions
related to hormone and lipid binding. Just how the highly conserved serpin architecture can support the multiple diverse functions
of PCI is a riddle best addressed by protein crystallography. Over the last few years we have solved the structure of PCI
in its native, cleaved and protein-complexed states. They reveal a conserved serpin fold and general mechanism of protease
inhibition, but with some unique features relating to inhibitory specificity/promiscuity, cofactor binding and hydrophobic
ligand transport.
Received 1 July 2008; received after revision 16 August 2008; accepted 22 August 2008 相似文献
8.
Three-dimensional structure of annexins 总被引:4,自引:0,他引:4
Annexins constitute a family of structurally related calcium- and phospholipid-binding proteins whose molecular structure
has been investigated in detail in the crystalline and membrane-bound form. Their polypeptide chain is folded into four or
eight α-helical domains of similar structure with a central hydrophilic pore. Bound to phospholipid membranes, the four-domain arrangement
of the annexin molecule is conserved. A peripheral binding mode has been well documented by electron microscopy and a variety
of other techniques. 相似文献
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Redox-regulated molecular chaperones 总被引:4,自引:0,他引:4
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Sobia Zaidi Md. Imtaiyaz Hassan Asimul Islam Faizan Ahmad 《Cellular and molecular life sciences : CMLS》2014,71(2):229-255
Cytochrome-c (cyt-c), a multi-functional protein, plays a significant role in the electron transport chain, and thus is indispensable in the energy-production process. Besides being an important component in apoptosis, it detoxifies reactive oxygen species. Two hundred and eighty-five complete amino acid sequences of cyt-c from different species are known. Sequence analysis suggests that the number of amino acid residues in most mitochondrial cyts-c is in the range 104?±?10, and amino acid residues at only few positions are highly conserved throughout evolution. These highly conserved residues are Cys14, Cys17, His18, Gly29, Pro30, Gly41, Asn52, Trp59, Tyr67, Leu68, Pro71, Pro76, Thr78, Met80, and Phe82. These are also known as “key residues”, which contribute significantly to the structure, function, folding, and stability of cyt-c. The three-dimensional structure of cyt-c from ten eukaryotic species have been determined using X-ray diffraction studies. Structure analysis suggests that the tertiary structure of cyt-c is almost preserved along the evolutionary scale. Furthermore, residues of N/C-terminal helices Gly6, Phe10, Leu94, and Tyr97 interact with each other in a specific manner, forming an evolutionary conserved interface. To understand the role of evolutionary conserved residues on structure, stability, and function, numerous studies have been performed in which these residues were substituted with different amino acids. In these studies, structure deals with the effect of mutation on secondary and tertiary structure measured by spectroscopic techniques; stability deals with the effect of mutation on T m (midpoint of heat denaturation), ?G D (Gibbs free energy change on denaturation) and folding; and function deals with the effect of mutation on electron transport, apoptosis, cell growth, and protein expression. In this review, we have compiled all these studies at one place. This compilation will be useful to biochemists and biophysicists interested in understanding the importance of conservation of certain residues throughout the evolution in preserving the structure, function, and stability in proteins. 相似文献
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Norin A Piersma SR Duine JA Jörnvall H 《Cellular and molecular life sciences : CMLS》2003,60(5):999-1006
The primary structure of nicotinoprotein alcohol dehydrogenase (ADH) from Amycolatopsis methanolica was determined and used for modelling against known ADH structures, and for evaluation of the coenzyme binding. The results establish the medium-chain dehydrogenase/reductase nature of the nicotinoprotein ADH. Its subunit model and that of the human class Ibeta ADH subunit structure are similar, with mean a carbon deviations of 0.95 A, but they differ in seven loops. Nicotinoprotein ADH occupies a phylogenetic position intermediate between the dimeric and tetrameric ADH families. Two of the differing loops are important for coenzyme binding in the nicotinoprotein model, where one (with a Thr271Arg exchange towards the traditional enzyme) may suggest a slight rotation of the coenzyme adenine ring in the nicotinoprotein, and the other, with an Asn288 insertion, may suggest an extra hydrogen bond to its nicotinamide ribose, favouring stronger binding of the coenzyme. Combined with previous data, this suggests differences in the details of the tight coenzyme binding in different nicotinoproteins, but a common mode for this binding by loop differences. 相似文献
13.
Justesen J Hartmann R Kjeldgaard NO 《Cellular and molecular life sciences : CMLS》2000,57(11):1593-1612
2'-5'-Oligoadenylate synthetase was among the first interferon-induced antiviral enzymes to be discovered. This family of enzymes plays an important role in the mechanisms of action of interferon antiviral activity, but is also involved in other cellular processes such as apoptosis and growth control. We have reviewed the function and genomic structure of this class of at least nine proteins. By studying the recently available data in the human genome database and the human Expressed Sequence Tag database, we have been able to build a comprehensive picture of the 2'-5'-oligoadenylate synthetase gene family and its precise location on chromosome 12. Chromosomal localization as well as the intron/exon structure of all four genes has been established and an overview of the splice variant forms of the 2'-5'-oligoadenylate synthetases arising from expression of the four genes is presented. Alignments of the human 2'-5'-oligoadenylate synthetase sequences with non-human 2'-5'-oligoadenylate synthetase sequences suggest that the exon structure and several amino acid sequence motifs have been conserved during evolution. 相似文献
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Sangeeta Chauhan Xinde Zheng Yue Ying Tan Boon-Hui Tay Shuhui Lim Byrappa Venkatesh Philipp Kaldis 《Cellular and molecular life sciences : CMLS》2012,69(22):3835-3850
Successful completion of the cell cycle relies on the precise activation and inactivation of cyclin-dependent kinases (Cdks) whose activity is mainly regulated by binding to cyclins. Recently, a new family of Cdk regulators termed Speedy/RINGO has been discovered, which can bind and activate Cdks but shares no apparent amino acid sequence homology with cyclins. All Speedy proteins share a conserved domain of approximately 140 amino acids called “Speedy Box”, which is essential for Cdk binding. Speedy/RINGO proteins display an important role in oocyte maturation in Xenopus. Interestingly, a common feature of all Speedy genes is their predominant expression in testis suggesting that meiotic functions may be the most important physiological feature of Speedy genes. Speedy homologs have been reported in mammals and can be traced back to the most primitive clade of chordates (Ciona intestinalis). Here, we investigated the evolution of the Speedy genes and have identified a number of new Speedy/RINGO proteins. Through extensive analysis of numerous species, we discovered diverse evolutionary histories: the number of Speedy genes varies considerably among species, with evidence of substantial gains and losses. Despite the interspecies variation, Speedy is conserved among most species examined. Our results provide a complete picture of the Speedy gene family and its evolution. 相似文献
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S. Leysen L. Vanderkelen S. D. Weeks C. W. Michiels S. V. Strelkov 《Cellular and molecular life sciences : CMLS》2013,70(6):1113-1122
Gram-negative bacteria can produce specific proteinaceous inhibitors to defend themselves against the lytic action of host lysozymes. So far, four different lysozyme inhibitor families have been identified. Here, we report the crystal structure of the Escherichia coli periplasmic lysozyme inhibitor of g-type lysozyme (PliG-Ec) in complex with Atlantic salmon g-type lysozyme (SalG) at a resolution of 0.95 Å, which is exceptionally high for a complex of two proteins. The structure reveals for the first time the mechanism of g-type lysozyme inhibition by the PliG family. The latter contains two specific conserved regions that are essential for its inhibitory activity. The inhibitory complex formation is based on a double ‘key-lock’ mechanism. The first key-lock element is formed by the insertion of two conserved PliG regions into the active site of the lysozyme. The second element is defined by a distinct pocket of PliG accommodating a lysozyme loop. Computational analysis indicates that this pocket represents a suitable site for small molecule binding, which opens an avenue for the development of novel antibacterial agents that suppress the inhibitory activity of PliG. 相似文献
17.
Starch-binding domains in the post-genome era 总被引:1,自引:1,他引:0
Starch belongs to the most abundant biopolymers on Earth. As a source of energy, starch is degraded by a large number of various
amylolytic enzymes. However, only about 10% of them are capable of binding and degrading raw starch. These enzymes usually
possess a distinct sequence-structural module, the so-called starchbinding domain (SBD). In general, all carbohydrate-binding
modules (CBMs) have been classified into the CBM families. In this sequence-based classification the individual types of SBDs
have been placed into seven CBM families: CBM20, CBM21, CBM25, CBM26, CBM34, CBM41 and CBM45. The family CBM20, known also
as a classical C-terminal SBD of microbial amylases, is the most thoroughly studied. The three-dimensional structures have
already been determined by X-ray crystallography or nuclear magnetic resonance for SBDs from five CBM families (20, 25, 26,
34 and 41), and the structure of the CBM21 has been modelled. Despite differences among the amino acid sequences, the fold
of a distorted β-barrel seems to be conserved together with a similar way of substrate binding (mainly stacking interactions
between aromatic residues and glucose rings). SBDs have recently been discovered in many non-amylolytic proteins. These may,
for example, have regulatory functions in starch metabolism in plants or glycogen metabolism in mammals. SBDs have also found
practical uses.
Received 25 May 2006; received after revision 26 June 2006; accepted 3 August 2006 相似文献
18.
Much effort has been devoted recently to expanding the amino acid repertoire in protein biosynthesis in vivo. From such experimental
work it has emerged that some of the non-canonical amino acids are accepted by the cellular translational machinery while
others are not, i.e. we have learned that some determinants must exist and that they can even be anticipated. Here, we propose
a conceptual framework by which it should be possible to assess deeper levels of the structure of the genetic code, and based
on this experiment to understand its evolution and establishment. First, we propose a standardised repertoire of 20 amino
acids as a basic set of conserved building blocks in protein biosynthesis in living cells to be the main criteria for genetic
code structure and evolutionary considerations. Second, based on such argumentation, we postulate the structure and evolution
of the genetic code in the form of three general statements: (i) the nature of the genetic code is deterministic; (ii) the
genetic code is conserved and universal; (iii) the genetic code is the oldest known level of complexity in the evolution of
living organisms that is accessible to our direct observation and experimental manipulations. Such statements are discussed
as our working hypotheses that are experimentally tested by recent findings in the field of expanded amino acid repertoire
in vivo.
Received 30 June 1999; accepted 9 July 1999 相似文献
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Grégoire Masliah Pierre Barraud Frédéric H. -T. Allain 《Cellular and molecular life sciences : CMLS》2013,70(11):1875-1895
The double-stranded RNA binding domain (dsRBD) is a small protein domain of 65–70 amino acids adopting an αβββα fold, whose central property is to bind to double-stranded RNA (dsRNA). This domain is present in proteins implicated in many aspects of cellular life, including antiviral response, RNA editing, RNA processing, RNA transport and, last but not least, RNA silencing. Even though proteins containing dsRBDs can bind to very specific dsRNA targets in vivo, the binding of dsRBDs to dsRNA is commonly believed to be shape-dependent rather than sequence-specific. Interestingly, recent structural information on dsRNA recognition by dsRBDs opens the possibility that this domain performs a direct readout of RNA sequence in the minor groove, allowing a global reconsideration of the principles describing dsRNA recognition by dsRBDs. We review in this article the current structural and molecular knowledge on dsRBDs, emphasizing the intricate relationship between the amino acid sequence, the structure of the domain and its RNA recognition capacity. We especially focus on the molecular determinants of dsRNA recognition and describe how sequence discrimination can be achieved by this type of domain. 相似文献