Molecular Species Compositions of Lung and Pancreas Phospholipids in the cftrtm1HGU/tm1HGU Cystic Fibrosis Mouse

Dombrowsky, Heike; Clark, Graeme T; Rau, Gunnar A.; Bernhard, Wolfgang; Postle, Anthony D.

doi:10.1203/01.pdr.0000049937.30305.8a

Cited by 34 publications

(28 citation statements)

References 27 publications

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“…The large positively-charged area on the surface of RSV M, which spans both domains, is consistent with the role of this protein in membrane association. We hypothesize that it is likely that this patch will be the driving force for association with the negatively-charged lung membrane (34,35). This deduction would be consistent with biochemical observations of other matrix-like proteins, where electrostatic charge is the major component of the interaction between protein and membrane, at least in vitro.…”

Section: Comparison Of Structures In Solution and In Crystalsupporting

confidence: 84%

Surface features of a Mononegavirales matrix protein indicate sites of membrane interaction

Money

McPhee²,

Mosely³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The matrix protein (M) of respiratory syncytial virus (RSV), the prototype viral member of the Pneumovirinae (family Paramyxoviridae, order Mononegavirales), has been crystallized and the structure determined to a resolution of 1.6 Å. The structure comprises 2 compact ␤-rich domains connected by a relatively unstructured linker region. Due to the high degree of side-chain order in the structure, an extensive contiguous area of positive surface charge covering Ϸ600 Å 2 can be resolved. This unusually large patch of positive surface potential spans both domains and the linker, and provides a mechanism for driving the interaction of the protein with a negatively-charged membrane surface or other virion components such as the nucleocapsid. This patch is complemented by regions of high hydrophobicity and a striking planar arrangement of tyrosine residues encircling the C-terminal domain. Comparison of the RSV M sequence with other members of the Pneumovirinae shows that regions of divergence correspond to surface exposed loops in the M structure, with the majority of viral species-specific differences occurring in the N-terminal domain.CD ͉ crystal structure ͉ respiratory syncytial virus ͉ sequence alignment R espiratory syncytial virus (RSV) is the prototype member of the Pneumovirinae, a subfamily of the Paramyxoviridae (order Mononegavirales). Morphologically, the extracellular virion consists of a lipid bilayer envelope, within which are embedded 3 glycoproteins, 2 of which (F and G) are important in cell attachment and viral entry into target cells. The third, the SH protein, contributes to pathology in the host (1). Internally, virions contain helical nucleocapsids that consist of N protein tightly bound to the negative-sense nonsegmented genomic RNA. The nucleocapsid in turn is associated with components of the viral RNA-dependent RNA polymerase (L, P, M2-1, and M2-2 proteins), forming the holo-nucleocapsid (2-4). Between the holo-nucleocapsid and the outer envelope there is a layer of matrix protein (M), which is associated peripherally with the membrane (5). The other family members of the Mononegavirales (Rhabdoviridae, Filoviridae, and Bornaviridae) all subscribe to this basic arrangement of the virion, although the overall morphology can vary between the families. For example, Paramyxoviridae virions are pleiomorphic, whereas the Rhabdoviridae have a regular bullet shape structure, and the Filoviridae have a more filamentous shape. Extracellular RSV virions form by a budding process that occurs at the plasma membrane within specialized lipid domains (5, 6) and M appears to drive the final assembly process, which is the incorporation of the holo-nucleocapsid and initiation of the budding process (7,8). Before budding, there is a coordinated assembly of viral components; and it is evident that the glycoproteins and M proteins are important determinants of the location on the plasma membrane at which the virus buds (9). It is also possible that the interaction between M and the glycoproteins, possibly mediat...

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Section: Comparison Of Structures In Solution and In Crystalsupporting

confidence: 84%

Surface features of a Mononegavirales matrix protein indicate sites of membrane interaction

Money

McPhee²,

Mosely³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…This profile is different from that usually present in typical nutritional EFA deficiency (9). Fatty acid composition may be influenced by genetic factors as shown in murine models (10,11) or in humans (12). The role played by pancreatic insufficiency may also be especially relevant because fat malabsorption persists in many patients despite pancreatic enzyme replacement (13).…”

mentioning

confidence: 98%

Persistence of Essential Fatty Acid Deficiency in Cystic Fibrosis Despite Nutritional Therapy

et al. 2009

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ABSTRACT:To study the evolution of plasma fatty acid composition of patients with cystic fibrosis (CF) in relation to nutritional status, pancreatic function, and development of CF-related liver disease (CFRLD) and diabetes mellitus, 24 CF pediatric patients with stable pulmonary disease were studied before and after an approximate period of 8 y. Nutritional status, pulmonary function, pancreatic function, and presence of CFRLD or diabetes mellitus were recorded. Results were compared with data obtained in 83 healthy children. Patients with CF have significantly lower linoleic acid (LA), docosahexaenoic acid (DHA), lignoceric acid, and LA ϫ DHA product and higher oleic acid, mead acid, dihomo-␥-linoleic acid, and docosapentaenoic acid (DPA). Comparison of samples taken at first and second studies revealed a significant decrease in LA levels and lignoceric acid associated with a significant increase in dihomo-␥-linoleic acid levels. Patients with CFRLD showed significantly higher mead acid/arachidonic acid ratio and lower total 6 polyunsaturated fatty acids content. There was no relation of plasma fatty acids composition with pancreatic function, pulmonary function, or diabetes mellitus. Follow-up of patients with CF shows that essential fatty acids deficiency, particularly in LA and DHA content, persisted unmodified along time despite an adequate nutritional therapy. Future studies after supplementation with 3 polyunsaturated fatty acids should be undertaken. (Pediatr Res 66: 585-589, 2009)

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“…Cystic fibrosis sufferers have considerably more 18:0 and less 16:0 in their PG than asthmatics do [49], implying that the PG in the LS of cystic fibrosis patients is less fluid than that of asthmatics. This trend is echoed in mice with CF, in which there are fewer docosahexaenoic in favour of arachidonic FARs compared to healthy controls [50].…”

Section: Lung Surfactantmentioning

confidence: 97%

Is phosphatidylglycerol essential for terrestrial life?

Furse

2016

J Chem Biol

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Lipids are of increasing importance in understanding biological systems. Lipids carrying an anionic charge are noted in particular for their electrostatic interactions with both proteins and divalent cations. However, the biological, analytical, chemical and biophysical data of such species are rarely considered together, limiting our ability to assess the true role of such lipids in vivo. In this review, evidence from a range of studies about the lipid phosphatidylglycerol is considered. This evidence supports the conclusions that this lipid is ubiquitous in living systems and generally of low abundance but probably fundamental for terrestrial life. Possible reasons for this are discussed and further questions posed.

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Molecular Species Compositions of Lung and Pancreas Phospholipids in the cftrtm1HGU/tm1HGU Cystic Fibrosis Mouse

Cited by 34 publications

References 27 publications

Surface features of a Mononegavirales matrix protein indicate sites of membrane interaction

Surface features of a Mononegavirales matrix protein indicate sites of membrane interaction

Persistence of Essential Fatty Acid Deficiency in Cystic Fibrosis Despite Nutritional Therapy

Is phosphatidylglycerol essential for terrestrial life?

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