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E de Leeuw

Publications and source records attributed to E de Leeuw.

10 recordsLinked to original sources
PubMed2001

Important role of the tetraloop region of 4.5S RNA in SRP binding to its receptor FtsY.

Binding of Escherichia coli signal recognition particle (SRP) to its receptor, FtsY, requires the presence of 4.5S RNA, although FtsY alone does not interact with 4.5S RNA. In this study, we report that the exchange of the GGAA tetraloop sequence in domain IV of 4.5S RNA for UUCG abolishes SRP-FtsY interaction, as determined by gel retardation and membrane targeting experiments, whereas replacements with other GNRA-type tetraloops have no effect. A number of other base exchanges in the tetraloop sequence have minor or intermediate inhibitory effects. Base pair disruptions in the stem adjacent to the tetraloop or replacement of the closing C-G base pair with G-C partially restored function of the otherwise inactive UUCG mutant. Chemical probing by hydroxyl radical cleavage of 4.5S RNA variants show that replacing GGAA with UUCG in the tetraloop sequence leads to structural changes both within the tetraloop and in the adjacent stem; the latter change is reversed upon reverting the C-G closing base pair to G-C. These results show that the SRP-FtsY interaction is strongly influenced by the structure of the tetraloop region of SRP RNA, in particular the tetraloop stem, and suggest that both SRP RNA and Ffh undergo mutual structural adaptation to form SRP that is functional in the interaction with the receptor, FtsY.

Amino Acid Substitution↗
PubMed2000

Anionic phospholipids are involved in membrane association of FtsY and stimulate its GTPase activity.

FtsY, the Escherichia coli homologue of the eukaryotic signal recognition particle (SRP) receptor alpha-subunit, is located in both the cytoplasm and inner membrane. It has been proposed that FtsY has a direct targeting function, but the mechanism of its association with the membrane is unclear. FtsY is composed of two hydrophilic domains: a highly charged N-terminal domain (the A-domain) and a C-terminal GTP-binding domain (the NG-domain). FtsY does not contain any hydrophobic sequence that might explain its affinity for the inner membrane, and a membrane-anchoring protein has not been detected. In this study, we provide evidence that FtsY interacts directly with E.coli phospholipids, with a preference for anionic phospholipids. The interaction involves at least two lipid-binding sites, one of which is present in the NG-domain. Lipid association induced a conformational change in FtsY and greatly enhanced its GTPase activity. We propose that lipid binding of FtsY is important for the regulation of SRP-mediated protein targeting.

Anions↗
PubMed1999

Molecular characterization of Escherichia coli FtsE and FtsX.

The genes ftsE and ftsX are organized in one operon together with ftsY. FtsY codes for the receptor of the signal recognition particle (SRP) that functions in targeting a subset of inner membrane proteins. We have found no indications for a structural relationship between FtsE/X and FtsY. Evidence is presented that FtsE and FtsX form a complex in the inner membrane that bears the characteristics of an ATP-binding cassette (ABC)-type transporter. FtsE is a hydrophilic nucleotide-binding protein that has a tendency to dimerize and associates with the inner membrane through an interaction with the integral membrane protein FtsX. An FtsE null mutant showed filamentous growth and appeared viable on high salt medium only, indicating a role for FtsE in cell division and/or salt transport.

ATP-Binding Cassette Transporters↗
PubMed1997

Membrane association of FtsY, the E. coli SRP receptor.

FtsY, the Escherichia coli homologue of the eukaryotic SRP receptor (SR alpha), is located both in the cytoplasm and in the inner membrane of E. coli. Similar to SR alpha, FtsY consists of two major domains: a strongly acidic N-terminal domain (A) and a C-terminal GTP binding domain (NG) of which the crystal structure has recently been determined. The domains were expressed both in vivo and in vitro to examine their subcellular localization. The results suggest that both domains associate with the membrane but that the nature of the association differs.

Bacterial Proteins↗
PubMed1996

Reason and protest in the new urban public health movement: an observation on the sociological analysis of political discourse in the 'healthy city'.

The urban environment represents an important social and geographical focus for the international new urban public health movement in general and the World Health Organization's 'Healthy Cities' project in particular. Existing and new policies of relevance to urban health are however infused with notions of cause, effect and ideas of appropriate intervention that reflect highly malleable and more or less conscious expressions of rationality, self-interest and organizational purpose--factors central to sociological analysis of the political discourse and objectives associated with the new urban public health movement. This article begins to develop a research agenda in this respect through consideration of the 'language' of policy and reference to Habermas' idea of 'communicative reason'. It is argued that case-study based research into the discourse of the new urban public health movement has to balance empirical accounts with analysis of the 'policy ontologies' that confront and underpin the mobilizations and has, secondly, to consider the 'communicative capacity and orientation' of such initiatives.

Communication↗
PubMed1995

European schools of public health in state of flux.

In 1992 there were in Europe 54 schools of public health and six out of eight possible structures were represented. To meet future needs two types (the US style school of public health as a stand-alone academic entity and the cross-school programme in public health with formal ties to national public health authorities) seem to be the most promising alternatives. New schools should strive to take on one of these shapes, and the rejuvenation of existing schools might, via accreditation procedures, evolve in those directions too.

Accreditation↗
PubMed1995

Health policy making: the Dutch experience.

The European Strategy for Health for All by the Year 2000 urged member states to develop a national health policy. In the developmental process of HFA2000 the notion of 'healthy public policy' was conceived in the framework of the WHO Health Promotion Programme. Such healthy public policy--simply referred to as 'health policy' in this article--would take health consequences in all governmental and societal realms into account. Health policy development in The Netherlands was laid down in a 1986 memorandum, 'Nota 2000'. The developmental process of the document is reviewed, and chances for factual implementation analysed. The article concludes with a list of actions to be pursued if health policy is to be successful.

Health Care Reform↗
PubMed1989

Concepts in health promotion: the notion of relativism.

'Health promotion' is a new and powerful concept. By some professionals in the field as well as by actors in the policy making spheres, though, the notion may be received with considerable scepticism. We have attributed this scepticism, as well as barriers to include notions of health promotion in day-to-day work, to a lack of knowledge of essential concepts in the health promotion context. In this article we first explore the quintessential nature of 'health' (a capacity of people, rather than an end product of medical care) before we set out to analyze some crucial components of health promotion: integral-ness, intersectorality, holism, and ecology. Integral intervention mixes appear to have synergetic, and therefore cost-effective, results. An intersectoral approach will be necessary to address all determinants of health in an adequate way. Alas, neither integral, nor intersectoral health programs have been documented in depth. The notions of holism and ecology seem to suffer from obscurantism and esoteric elitism, though commendable in their scope. Here, we introduce 'relativism' to combine various valuable approaches into one more comprehensive scheme. Moreover, a 'relativist' approach to health promotion might induce better and more fruitful cooperation among professions. Finally, some research gaps have been identified. Policy development studies remain to have top priority in development of health promotion. Better documentation of efforts in this field will be of crucial importance. Further development of, and research on how to apply relativist approaches may be recommended. Cooperation, and opening up a dialogue between different professions and actors is of great importance in this field.

Ecology↗