Structural characterization of a novel monotreme-specific protein with antimicrobial activity from the milk of the platypus

Newman, Janet; Sharp, Julie A.; Enjapoori, Ashwantha Kumar; Bentley, John D.; Nicholas, Kevin R.; Adams, Timothy E.; Peat, Thomas S.

doi:10.1107/s2053230x17017708

Cited by 12 publications

(5 citation statements)

References 27 publications

(26 reference statements)

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“…platypus LEG1c/MLP protein has been structurally resolved 38 . Based on the information provided, other LEG1 protein structures from representative vertebrates were predicted using the Phyre2 tool.…”

Section: Structural Prediction Implies That Leg1 Might Retain a Consementioning

confidence: 99%

Evolutionary and Molecular Characterization of liver-enriched gene 1

Dang

Wang

Liu

et al. 2020

Sci Rep

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Liver-enriched gene 1 (Leg1) is a newly identified gene with little available functional information. To evolutionarily and molecularly characterize Leg1 genes, a phylogenetic study was first conducted, which indicated that Leg1 is a conserved gene that exists from bacteria to mammals. During the evolution of mammals, Leg1s underwent tandem duplications, which gave rise to Leg1a, Leg1b, and Leg1c clades. Analysis of the pig genome showed the presence of all three paralogs of pig Leg1 genes (pLeg1s), whereas only Leg1a could be found in the human (hLeg1a) or mouse (mLeg1a) genomes. purifying force acts on the evolution of Leg1 genes, likely subjecting them to functional constraint. Molecularly, pLeg1a and its coded protein, pig LEG1a (pLEG1a), displayed high similarities to its human and mouse homologs in terms of gene organization, expression patterns, and structures. Hence, pLeg1a, hLeg1a, and mLeg1a might preserve similar functions. Additionally, expression analysis of the three Leg1as suggested that eutherian Leg1as might have different functions from those of zebrafish and platypus due to subfunctionalization. Therefore, pLeg1a might provide essential information about eutherian Leg1a. Moreover, a preliminary functional study using RNA-seq suggested that pLeg1a is involved in the lipid homeostasis. In conclusion, our study provides some basic information on the aspects of evolution and molecular function, which could be applied for further validation of Leg1 using pig models. Leg1 (liver-enriched gene 1, or C6orf58 homolog) is a newly identified gene with very little available functional information 1,2. It is characterized by the presence of Domain of Unknown Function 781 (DUF781 or LEG1 domain) in its encoded protein 1,2. Leg1 was first identified in a zebrafish (Danio rerio) microarray study, in which it was named on the basis of its abundance in the liver 3. Functional experiments later demonstrated that Leg1 is involved in liver development, as knock-down of Leg1 in embryos results in small liver phenotype due to blocked liver expansion 1. Another functional study of the Leg1 gene was performed in the platypus (Ornithorhynchus anatinus), in which the human C6orf58 paralog MLP encodes monotreme lactation protein (MLP). MLP protein is a secreted protein that is enriched in milk, where it can exert antibacterial activity. Thus, it is presumed that MLP is related to the innate immunity of monotremes during the nipple-less delivery of milk to the hatchlings 2. Proteomic studies in eutherian species revealed that the Leg1-encoded N-glycosylated LEG1 protein is mainly present in saliva and seminal plasma 4,5. However, no further functional studies were carried out in eutherian animals. Expression profiling analyses of mouse (Mus musculus) and human (Homo sapiens) Leg1s (mLeg1 and hLeg1) reported in the Expression Atlas (www.ebi.ac.uk/gxa/home) showed that the gene is not expressed in the liver or mammary glands, in contrast to studies in monotremes and fishes, implying that eutherian Leg1s might have different ...

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Section: Structural Prediction Implies That Leg1 Might Retain a Consementioning

confidence: 99%

Evolutionary and Molecular Characterization of liver-enriched gene 1

Dang

Wang

Liu

et al. 2020

Sci Rep

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“…Monotremes express a unique monotreme lactation protein (MLP) in a variety of tissues including milk, with the highest expression occurring in milk cells (Enjapoori et al, 2014). Analysis of the recombinant protein shows it is N-glycosylated, amphipathic and a-helical, and therefore typical of an antimicrobial protein (Enjapoori et al, 2014;Newman et al, 2018). Functional studies have confirmed the recombinant protein has antimicrobial properties against Staphylococcus aureus and a commensal bacteria, Enterococcus faecalis (Enjapoori et al, 2014).…”

Section: Milk Aids Immunological Defense Of the Youngmentioning

confidence: 99%

Marsupial and monotreme milk—a review of its nutrient and immune properties

Stannard

Miller

Old

2020

PeerJ

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All mammals are characterized by the ability of females to produce milk. Marsupial (metatherian) and monotreme (prototherian) young are born in a highly altricial state and rely on their mother’s milk for the first part of their life. Here we review the role and importance of milk in marsupial and monotreme development. Milk is the primary source of sustenance for young marsupials and monotremes and its composition varies at different stages of development. We applied nutritional geometry techniques to a limited number of species with values available to analyze changes in macronutrient composition of milk at different stages. Macronutrient energy composition of marsupial milk varies between species and changes concentration during the course of lactation. As well as nourishment, marsupial and monotreme milk supplies growth and immune factors. Neonates are unable to mount a specific immune response shortly after birth and therefore rely on immunoglobulins, immunological cells and other immunologically important molecules transferred through milk. Milk is also essential to the development of the maternal-young bond and is achieved through feedback systems and odor preferences in eutherian mammals. However, we have much to learn about the role of milk in marsupial and monotreme mother-young bonding. Further research is warranted in gaining a better understanding of the role of milk as a source of nutrition, developmental factors and immunity, in a broader range of marsupial species, and monotremes.

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“…Monotremes express a unique monotreme lactation protein (MLP) in a variety of tissues including milk, with the highest expression occurring in milk cells (Enjapoori et al 2014). Analysis of the recombinant protein shows it is N-glycosylated, amphipathic and -helical, and therefore typical of an antimicrobial protein (Enjapoori et al 2014;Newman et al 2018). Functional studies have confirmed the recombinant protein has antimicrobial properties against Staphylococcus aureus and a commensal bacteria, Enterococcus faecalis (Enjapoori et al 2014).…”

Section: Milk Aids Immunological Defense Of the Youngmentioning

confidence: 99%

Peer Review #1 of "Marsupial and monotreme milk—a review of its nutrient and immune properties (v0.1)"

2020

View full text Add to dashboard Cite

All mammals are characterized by the ability of females to produce milk. Marsupial (metatherian) and monotreme (prototherian) young are born in a highly altricial state and rely on their mother's milk for the first part of their life. Here we review the role and importance of milk in marsupial and monotreme development. Milk is the primary source of sustenance for young marsupials and monotremes and its composition varies at different stages of development. We applied nutritional geometry techniques to a limited number of species with values available to analyze changes in macronutrient composition of milk at different stages. Macronutrient energy composition of marsupial milk varies between species and changes concentration during the course of lactation. As well as nourishment, marsupial and monotreme milk supplies growth and immune factors. Neonates are unable to mount a specific immune response shortly after birth and therefore rely on immunoglobulins, immunological cells and other immunologically important molecules transferred through milk. Milk is also essential to the development of the maternal-young bond and is achieved through feedback systems and odor preferences in eutherian mammals. However, we have much to learn about the role of milk in marsupial and monotreme mother-young bonding. Further research is warranted in gaining a better understanding of the role of milk as a source of nutrition, developmental factors and immunity, in a broader range of marsupial species, and monotremes.

show abstract

Structural characterization of a novel monotreme-specific protein with antimicrobial activity from the milk of the platypus

Cited by 12 publications

References 27 publications

Evolutionary and Molecular Characterization of liver-enriched gene 1

Evolutionary and Molecular Characterization of liver-enriched gene 1

Marsupial and monotreme milk—a review of its nutrient and immune properties

Peer Review #1 of "Marsupial and monotreme milk—a review of its nutrient and immune properties (v0.1)"

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