PPLRE Corpus 7181.a

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Related Examples

• PPLRE Corpus 7181.a.5.
• PPLRE Corpus 7181.a.2,4-5.
• PPLRE Corpus 7181.a.t,1-2,5-6.

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=Raw

Title

• Interaction between Polyketide Synthase and Transporter Suggests Coupled Synthesis and Export of Virulence Lipid in M. tuberculosis.

Abstract

Virulent mycobacteria utilize surface-exposed polyketides to interact with host cells, but the mechanism by which these hydrophobic molecules are transported across the cell envelope to the surface of the bacteria is poorly understood. Phthiocerol dimycocerosate (PDIM), a surface-exposed polyketide lipid necessary for Mycobacterium tuberculosis virulence, is the product of several polyketide synthases including PpsE. Transport of PDIM requires MmpL7, a member of the MmpL family of RND permeases. Here we show that a domain of MmpL7 biochemically interacts with PpsE, the first report of an interaction between a biosynthetic enzyme and its cognate transporter. Overexpression of the interaction domain of MmpL7 acts as a dominant negative to PDIM synthesis by poisoning the interaction between synthase and transporter. This suggests that MmpL7 acts in complex with the synthesis machinery to efficiently transport PDIM across the cell membrane. Coordination of synthesis and transport may not only be a feature of MmpL-mediated transport in M. tuberculosis., but may also represent a general mechanism of polyketide export in many different microorganisms.

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=NER (Simple)

Title

• Interaction between Polyketide Synthase and Transporter Suggests Coupled Synthesis and Export of Virulence Lipid in M. tuberculosis<ORGANISM_1>.

Abstract

• Virulent mycobacteria utilize surface-exposed polyketides to interact with host cells, but the mechanism by which these hydrophobic molecules are transported across the cell envelope to the surface of the bacteria is poorly understood.
• Phthiocerol dimycocerosate (PDIM<NamedEntity_1>), a surface-exposed polyketide lipid necessary for Mycobacterium tuberculosis<ORGANISM_1>> virulence, is the product of several polyketide synthases including PpsE.
• Transport of PDIM requires MmpL7<PROTEIN_1>, a member of the MmpL family of RND permeases.
• Here we show that a domain of MmpL7<PROTEIN_1> biochemically interacts with PpsE, the first report of an interaction between a biosynthetic enzyme and its cognate transporter.
• Overexpression of the interaction domain of MmpL7<PROTEIN_1> acts as a dominant negative to PDIM<NamedEntity_1> synthesis by poisoning the interaction between synthase and transporter.
• This suggests that MmpL7<PROTEIN_1> acts in complex with the synthesis machinery to efficiently transport PDIM<NamedEntity_1> across the cell membrane.
• Coordination of synthesis and transport may not only be a feature of MmpL-mediated transport in M. tuberculosis<ORGANISM_1>., but may also represent a general mechanism of polyketide export in many different microorganisms.

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=Annotated

RowID

Token

Stemmed

POS

Parse Tree

Concept Type

Concept ID

Predicate

SRL-1

SRL-2

SRL-3

SRL-4

1

Virulent

Virulent

JJ

(S1(S(S(NP*

(mono_cell

(0

(2

*

(A0*

*

*

*

2

mycobacteria

mycobacteria

NNS

*)

)

)

)

*

*)

*

*

*

3

utilize

utilize

VB

(VP*

Functional_Concept

C0042153

4

utilize

(V*)

*

*

*

4

surface-exposed

surface-exposed

JJ

(NP*

Spatial_Concept

C0205148

4

*

(A1*

*

*

*

5

polyketides

polyketides

NNS

*)

Clinical_Attribute

C0332157

4

*

*)

*

*

*

6

to

to

TO

(S(VP*

-

-

-

*

(AM-PNC*

*

*

*

7

interact

interact

VB

(VP*

Molecular_Function

C0687133

4

interact

*

(V*)

*

*

8

with

with

IN

(PP*

-

-

-

*

*

(A2*

*

*

9

host

host

NN

(NP*

(cell_type

(1

(2

*

*

*

*

*

10

cells

cell

NNS

*)))))))

)

)

)

*

*)

*)

*

*

11

,

,

,

*

-

-

-

*

*

*

*

*

12

but

but

CC

*

-

-

-

*

*

*

*

*

13

the

the

DT

(S(NP(NP*

-

-

-

*

*

*

(AM-MNR*

(A1*

14

mechanism

mechanism

NN

*)

Functional_Concept

C0441712

4

*

*

*

*)

*

15

by

by

IN

(SBAR(WHPP*

-

-

-

*

*

*

*

*

16

which

which

WDT

(WHNP*))

-

-

-

*

*

*

*

*

17

these

these

DT

(S(NP*

-

-

-

*

*

*

(A1*

*

18

hydrophobic

hydrophobic

JJ

*

(peptide

(2

(2

*

*

*

*

*

19

molecules

molecule

NNS

*)

)

)

)

*

*

*

*)

*

20

are

are

AUX

(VP*

-

-

-

*

*

*

*

*

21

transported

transport

VBN

(VP*

Cell_Function

C0005528

4

transported

*

*

(V*)

*

22

across

across

IN

(PP*

-

-

-

*

*

*

*

*

23

the

the

DT

(NP*

-

-

-

*

*

*

*

*

24

cell

cell

NN

*

(LOCALIZATION

(GO0005618

(3

*

*

*

*

*

25

envelope

envelope

NN

*))

)

)

)

*

*

*

*

*

26

to

to

TO

(PP*

-

-

-

*

*

*

*

*

27

the

the

DT

(NP(NP*

-

-

-

*

*

*

*

*

28

surface

surface

NN

*)

Spatial_Concept

C0205148

4

*

*

*

*

*

29

of

of

IN

(PP*

-

-

-

*

*

*

*

*

30

the

the

DT

(NP*

-

-

-

*

*

*

*

*

31

bacteria

bacteria

NNS

*)))))))))

mono_cell

4

2

*

*

*

*

*)

32

is

is

AUX

(VP*

-

-

-

*

*

*

*

*

33

poorly

poorly

RB

(ADVP*)

Qualitative_Concept

C0205169

4

*

*

*

*

(AM-MNR*)

34

understood

understand

VBN

(VP*)))

Mental_Process

C0162340

4

understood

*

*

*

(V*)

35

.

.

.

*))

-

-

-

*

*

36

37

Phthiocerol

Phthiocerol

NNP

(S1(S(NP(NP*

(Lipid

(C0070976

(4

*

*

38

dimycocerosate

dimycocerosate

NNP

*)

)

)

)

*

*

39

(

(

-LRB-

(PRN*

-

-

-

*

*

40

PDIM

PDIM

NNP

(NP*)

other_organic_compound

6

2

*

*

41

)

)

-RRB-

*)

-

-

-

*

*

42

,

,

,

*

-

-

-

*

*

43

a

a

DT

(NP(NP*

-

-

-

*

*

44

surface-exposed

surface-exposed

JJ

*

lipid

7

2

*

*

45

polyketide

polyketide

JJ

*

-

-

-

*

*

46

lipid

lipid

NN

*)

14742191

1

5

*

*

47

necessary

necessary

JJ

(ADJP*

Lipid

C0023779

4

*

*

48

for

for

IN

(PP*

639871

3

*

*

49

Mycobacterium

Mycobacterium

NNP

(NP*

(ORGANISM

(1773

(3

*

*

50

tuberculosis

tuberculosis

FW

*

)

)

)

*

*

51

virulence

virulence

NN

*))))

Biologic_Function

C0042765

4

*

*

52

,

,

,

*)

-

-

-

*

*

53

is

is

AUX

(VP*

-

-

-

*

*

54

the

the

DT

(NP(NP*

-

-

-

*

*

55

product

product

NN

*)

3707459

1

5

*

*

56

of

of

IN

(PP*

-

-

-

*

*

57

several

several

JJ

(NP(NP*

Quantitative_Concept

C0443302

4

*

(A2*

58

polyketide

polyketide

JJ

*

(PROTEIN

(localID_0

(1

*

*

59

synthases

synthases

NNS

*)

)

)

)

*

*)

60

including

include

VBG

(PP*

Functional_Concept

C0332257

4

including

(V*)

61

PpsE

PpsE

NNP

(NP*))))))

PROTEIN

localID_1

1

*

(A1*)

62

.

.

.

*))

-

-

-

*

*

63

64

Transport

Transport

NNP

(S1(S(NP(NP*)

Cell_Function

C0005528

4

*

(A1*

65

of

of

IN

(PP*

-

-

-

*

*

66

PDIM

PDIM

NNP

(NP*)))

PROTEIN

localID_2

1

*

*)

67

requires

require

VBZ

(VP*

2602586

1

5

requires

(V*)

68

MmpL7

MmpL7

NNP

(NP(NP*)

PROTEIN

localID_3

1

*

(A0*

69

,

,

,

*

-

-

-

*

*

70

a

a

DT

(NP(NP*

-

-

-

*

*

71

member

member

NN

*)

Population_Group

C0680022

4

*

*

72

of

of

IN

(PP*

-

-

-

*

*

73

the

the

DT

(NP(NP*

-

-

-

*

*

74

MmpL

MmpL

NNP

*

(PROTEIN

(localID_4

(1

*

*

75

family

family

NN

*)

)

)

)

*

*

76

of

of

IN

(PP*

-

-

-

*

*

77

RND

RND

JJ

(NP*

(PROTEIN

(localID_5

(1

*

*

78

permeases

permeases

NNS

*)))))))

)

)

)

*

*)

79

.

.

.

*))

-

-

-

*

*

*

80

81

Here

Here

RB

(S1(S(ADVP*)

109485

1

5

*

(AM-LOC*)

*

82

we

we

PRP

(NP*)

-

-

-

*

(A0*)

*

83

show

show

VBP

(VP*

656725

2

5

show

(V*)

*

84

that

that

IN

(SBAR*

-

-

-

*

(A1*

*

85

a

a

DT

(S(NP(NP*

-

-

-

*

*

(A1*

86

domain

domain

NN

*)

8437765

2

5

*

*

*

87

of

of

IN

(PP*

-

-

-

*

*

*

88

MmpL7

MmpL7

NNP

(NP*)))

PROTEIN

localID_3

1

*

*

*)

89

biochemically

biochemically

RB

(ADVP*)

Functional_Concept

C0205474

4

*

*

(AM-ADV*)

90

interacts

interact

VBZ

(VP*

Molecular_Function

C0687133

4

interacts

*

(V*)

91

with

with

IN

(PP*

-

-

-

*

*

(A2*

92

PpsE

PpsE

NNP

(NP(NP*)

PROTEIN

localID_1

1

*

*

*

93

,

,

,

*

-

-

-

*

*

*

94

the

the

DT

(NP(NP*

-

-

-

*

*

*

95

first

first

JJ

*

Quantitative_Concept

C0205435

4

*

*

*

96

report

report

NN

*)

Intellectual_Product

C0684224

4

*

*

*

97

of

of

IN

(PP*

-

-

-

*

*

*

98

an

an

DT

(NP(NP*

-

-

-

*

*

*

99

interaction

interaction

NN

*)

Molecular_Function

C0687133

4

*

*

*

100

between

between

IN

(PP*

-

-

-

*

*

*

101

a

a

DT

(NP(NP*

-

-

-

*

*

*

102

biosynthetic

biosynthetic

JJ

*

-

-

-

*

*

*

103

enzyme

enzyme

NN

*)

PROTEIN

638536

3

*

*

*

104

and

and

CC

*

-

-

-

*

*

*

105

its

its

PRP$

(NP*

-

-

-

*

*

*

106

cognate

cognate

JJ

*

2042649

1

5

*

*

*

107

transporter

transporter

NN

*))))))))))))

PROTEIN

localID_6

1

*

*)

*)

108

.

.

.

*))

-

-

-

*

*

*

109

110

Overexpression

Overexpression

NN

(S1(S(NP(NP*)

Genetic_Function

C1514559

4

*

(A0*

*

111

of

of

IN

(PP*

-

-

-

*

*

*

112

the

the

DT

(NP(NP*

-

-

-

*

*

*

113

interaction

interaction

JJ

*

(protein_domain_or_region

(16

(2

*

*

*

114

domain

domain

NN

*)

)

)

)

*

*

*

115

of

of

IN

(PP*

-

-

-

*

*

*

116

MmpL7

MmpL7

NNP

(NP*)))))

PROTEIN

localID_3

1

*

*)

*

117

acts

act

VBZ

(VP*

Laboratory_Procedure

C0427611

4

acts

(V*)

*

118

as

as

IN

(PP*

-

-

-

*

(A1*

*

119

a

a

DT

(NP*

-

-

-

*

*

*

120

dominant

dominant

JJ

*

829524

1

5

*

*

*

121

negative

negative

NN

*))

Qualitative_Concept

C0205160

4

*

*

*

122

to

to

TO

(S(VP*

-

-

-

*

*

*

123

PDIM

PDIM

VB

(VP*

PROTEIN

localID_2

1

PDIM

*

(V*)

124

synthesis

synthesis

NN

(NP*)

Phenomenon_or_Process

C0869032

4

*

*

(A1*)

125

by

by

IN

(PP*

-

-

-

*

*

(A2*

126

poisoning

poisoning

NN

(NP*))

Injury_or_Poisoning

C0032343

4

*

*

*)

127

the

the

DT

(NP(NP*

-

-

-

*

*

(A1*

128

interaction

interaction

NN

*)

Finding

C0037420

4

*

*

*

129

between

between

IN

(PP*

-

-

-

*

*

*

130

synthase

synthase

NN

(NP*

(PROTEIN

(localID_7

(1

*

*

*

131

and

and

CC

*

)

)

)

*

*

*

132

transporter

transporter

NN

*)))))))

-

-

-

*

*)

*)

133

.

.

.

*))

-

-

-

*

*

*

*

134

135

This

This

DT

(S1(S(NP*)

-

-

-

*

(A0*)

*

*

136

suggests

suggest

VBZ

(VP*

Finding

C0424012

4

suggests

(V*)

*

*

137

that

that

IN

(SBAR*

-

-

-

*

(A1*

*

*

138

MmpL7

MmpL7

NNP

(S(NP*)

PROTEIN

localID_3

1

*

*

(A0*)

*

139

acts

act

VBZ

(VP*

Laboratory_Procedure

C0427611

4

acts

*

(V*)

*

140

in

in

IN

(PP*

-

-

-

*

*

*

*

141

complex

complex

NN

(NP(NP*)

Qualitative_Concept

C0439855

4

*

*

*

*

142

with

with

IN

(PP*

-

-

-

*

*

*

*

143

the

the

DT

(NP*

-

-

-

*

*

*

*

144

synthesis

synthesis

NN

*

Phenomenon_or_Process

C0869032

4

*

*

*

*

145

machinery

machinery

NN

*))))

Manufactured_Object

C0337076

4

*

*

*

*

146

to

to

TO

(S(VP*

-

-

-

*

*

*

*

147

efficiently

efficiently

RB

(VP(ADVP*)

Qualitative_Concept

C0442799

4

*

*

*

(AM-MNR*)

148

transport

transport

VB

*

Cell_Function

C0005528

4

transport

*

*

(V*)

149

PDIM

PDIM

NNP

(NP*)

other_name

6

2

*

*

*

(A1*

150

across

across

IN

(PP*

-

-

-

*

*

*

*

151

the

the

DT

(NP*

-

-

-

*

*

*

*

152

cell

cell

NN

*

(LOCALIZATION

(GO0005886

(3

*

*

*

*

153

membrane

membrane

NN

*)))))))))

)

)

)

*

*)

*

*)

154

.

.

.

*))

-

-

-

*

*

155

156

Coordination

Coordination

NN

(S1(S(NP(NP*)

Physiologic_Function

C0242414

4

*

(A0*

157

of

of

IN

(PP*

-

-

-

*

*

158

synthesis

synthesis

NN

(NP*

Phenomenon_or_Process

C0869032

4

*

*

159

and

and

CC

*

-

-

-

*

*

160

transport

transport

NN

*)))

Cell_Function

C0005528

4

*

*)

161

may

may

MD

(VP(VP*

-

-

-

*

*

162

not

not

RB

*

(00025615

(1

(5

*

*

163

only

only

RB

(ADVP*)

)

)

)

*

*

164

be

be

AUX

(VP*

-

-

-

*

*

165

a

a

DT

(NP(NP*

-

-

-

*

*

166

feature

feature

NN

*)

5776742

1

5

*

*

167

of

of

IN

(PP*

-

-

-

*

*

168

MmpL-mediated

MmpL-mediated

JJ

(NP(NP*

-

-

-

*

*

169

transport

transport

NN

*)

Social_Behavior

C0086597

4

*

*

170

in

in

IN

(PP*

-

-

-

*

*

171

M.

M.

NNP

(NP*

(ORGANISM

(1773

(3

*

*

172

tuberculosis

tuberculosis

NNS

*)))))))

)

)

)

*

*

173

,

,

,

*

-

-

-

*

*

174

but

but

CC

*

-

-

-

*

*

175

may

may

MD

(VP*

-

-

-

*

(AM-MOD*)

176

also

also

RB

(ADVP*)

47757

1

5

*

(AM-DIS*)

177

represent

represent

VB

(VP*

1671008

9

5

represent

(V*)

178

a

a

DT

(NP(NP*

-

-

-

*

(A1*

179

general

general

JJ

*

Spatial_Concept

C0205246

4

*

*

180

mechanism

mechanism

NN

*)

Functional_Concept

C0441712

4

*

*

181

of

of

IN

(PP*

-

-

-

*

*

182

polyketide

polyketide

JJ

(NP*

-

-

-

*

*

183

export

export

NN

*)))

Occupational_Activity

C0699789

4

*

*

184

in

in

IN

(PP*

-

-

-

*

*

185

many

many

JJ

(NP*

1607490

1

5

*

*

186

different

different

JJ

*

Qualitative_Concept

C0443199

4

*

*

187

microorganisms

microorganism

NNS

*)))))

mono_cell

22

2

*

*)

188

.

.

.

*))

-

-

-

---