PPLRE Corpus 7181.a

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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.


=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.

=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 . . . *)) - - -