Conformational changes in the endosomal sorting complex required for the transport III subunit Ist1 lead to distinct modes of ATPase Vps4 regulation
Jason Tan, Brian A. Davies, Johanna A. Payne, Linda M. Benson, David J. Katzmann
Intralumenal vesicle formation of the multivesicular body is a critical step in the delivery of endocytic cargoes to the lysosome for degradation. Endosomal sorting complex required for transport III (ESCRT-III) subunits polymerize on endosomal membranes to facilitate membrane budding away from the cytoplasm to generate these intralumenal vesicles. The ATPase Vps4 remodels and disassembles ESCRT-III, but the manner in which Vps4 activity is coordinated with ESCRT-III function remains unclear. Ist1 is structurally homologous to ESCRT-III subunits and has been reported to inhibit Vps4 function despite the presence of a microtubule-interacting and trafficking domain-interacting motif (MIM) capable of stimulating Vps4 in the context of other ESCRT-III subunits. Here we report that Ist1 inhibition of Vps4 ATPase activity involves two elements in Ist1: the MIM itself and a surface containing a conserved ELYC sequence. In contrast, the MI Minteraction, in concert with a more open conformation of the Ist1 core, resulted in stimulation of Vps4. Addition of the ESCRT-III subunit binding partner of Ist1, Did2, also converted Ist1 from an inhibitor to a stimulator of Vps4 ATPase activity. Finally, distinct regulation of Vps4 by Ist1 corresponded with altered ESCRT-III disassembly in vitro. Together, these data support a model in which Ist1-Did2 interactions during ESCRT-III polymerization coordinate Vps4 activity with the timing of ESCRT-III disassembly.
https://doi.org/10.1074/jbc.M115.665604
10.1074/jbc.M115.665604
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Endosomal Sorting Complexes Required for Transport Medicine & Life Sciences
Adenosine Triphosphatases Medicine & Life Sciences
Membranes Chemical Compounds
Multivesicular Bodies Medicine & Life Sciences
Conformations Chemical Compounds
Conserved Sequence Medicine & Life Sciences
Polymerization Chemical Compounds
Lysosomes Medicine & Life Sciences
Tan, J., Davies, B. A., Payne, J. A., Benson, L. M., & Katzmann, D. J. (2015). Conformational changes in the endosomal sorting complex required for the transport III subunit Ist1 lead to distinct modes of ATPase Vps4 regulation. Journal of Biological Chemistry, 290(50), 30053-30065. https://doi.org/10.1074/jbc.M115.665604
Conformational changes in the endosomal sorting complex required for the transport III subunit Ist1 lead to distinct modes of ATPase Vps4 regulation. / Tan, Jason; Davies, Brian A.; Payne, Johanna A.; Benson, Linda M.; Katzmann, David J.
In: Journal of Biological Chemistry, Vol. 290, No. 50, 11.12.2015, p. 30053-30065.
Tan, J, Davies, BA, Payne, JA, Benson, LM & Katzmann, DJ 2015, 'Conformational changes in the endosomal sorting complex required for the transport III subunit Ist1 lead to distinct modes of ATPase Vps4 regulation', Journal of Biological Chemistry, vol. 290, no. 50, pp. 30053-30065. https://doi.org/10.1074/jbc.M115.665604
Tan J, Davies BA, Payne JA, Benson LM, Katzmann DJ. Conformational changes in the endosomal sorting complex required for the transport III subunit Ist1 lead to distinct modes of ATPase Vps4 regulation. Journal of Biological Chemistry. 2015 Dec 11;290(50):30053-30065. https://doi.org/10.1074/jbc.M115.665604
Tan, Jason ; Davies, Brian A. ; Payne, Johanna A. ; Benson, Linda M. ; Katzmann, David J. / Conformational changes in the endosomal sorting complex required for the transport III subunit Ist1 lead to distinct modes of ATPase Vps4 regulation. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 50. pp. 30053-30065.
@article{48965d4995d44230bf827bd708c56238,
title = "Conformational changes in the endosomal sorting complex required for the transport III subunit Ist1 lead to distinct modes of ATPase Vps4 regulation",
abstract = "Intralumenal vesicle formation of the multivesicular body is a critical step in the delivery of endocytic cargoes to the lysosome for degradation. Endosomal sorting complex required for transport III (ESCRT-III) subunits polymerize on endosomal membranes to facilitate membrane budding away from the cytoplasm to generate these intralumenal vesicles. The ATPase Vps4 remodels and disassembles ESCRT-III, but the manner in which Vps4 activity is coordinated with ESCRT-III function remains unclear. Ist1 is structurally homologous to ESCRT-III subunits and has been reported to inhibit Vps4 function despite the presence of a microtubule-interacting and trafficking domain-interacting motif (MIM) capable of stimulating Vps4 in the context of other ESCRT-III subunits. Here we report that Ist1 inhibition of Vps4 ATPase activity involves two elements in Ist1: the MIM itself and a surface containing a conserved ELYC sequence. In contrast, the MI Minteraction, in concert with a more open conformation of the Ist1 core, resulted in stimulation of Vps4. Addition of the ESCRT-III subunit binding partner of Ist1, Did2, also converted Ist1 from an inhibitor to a stimulator of Vps4 ATPase activity. Finally, distinct regulation of Vps4 by Ist1 corresponded with altered ESCRT-III disassembly in vitro. Together, these data support a model in which Ist1-Did2 interactions during ESCRT-III polymerization coordinate Vps4 activity with the timing of ESCRT-III disassembly.",
author = "Jason Tan and Davies, {Brian A.} and Payne, {Johanna A.} and Benson, {Linda M.} and Katzmann, {David J.}",
note = "Publisher Copyright: {\textcopyright} 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Copyright: Copyright 2015 Elsevier B.V., All rights reserved.",
doi = "10.1074/jbc.M115.665604",
T1 - Conformational changes in the endosomal sorting complex required for the transport III subunit Ist1 lead to distinct modes of ATPase Vps4 regulation
AU - Tan, Jason
AU - Davies, Brian A.
AU - Payne, Johanna A.
AU - Benson, Linda M.
AU - Katzmann, David J.
N1 - Publisher Copyright: © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Copyright: Copyright 2015 Elsevier B.V., All rights reserved.
N2 - Intralumenal vesicle formation of the multivesicular body is a critical step in the delivery of endocytic cargoes to the lysosome for degradation. Endosomal sorting complex required for transport III (ESCRT-III) subunits polymerize on endosomal membranes to facilitate membrane budding away from the cytoplasm to generate these intralumenal vesicles. The ATPase Vps4 remodels and disassembles ESCRT-III, but the manner in which Vps4 activity is coordinated with ESCRT-III function remains unclear. Ist1 is structurally homologous to ESCRT-III subunits and has been reported to inhibit Vps4 function despite the presence of a microtubule-interacting and trafficking domain-interacting motif (MIM) capable of stimulating Vps4 in the context of other ESCRT-III subunits. Here we report that Ist1 inhibition of Vps4 ATPase activity involves two elements in Ist1: the MIM itself and a surface containing a conserved ELYC sequence. In contrast, the MI Minteraction, in concert with a more open conformation of the Ist1 core, resulted in stimulation of Vps4. Addition of the ESCRT-III subunit binding partner of Ist1, Did2, also converted Ist1 from an inhibitor to a stimulator of Vps4 ATPase activity. Finally, distinct regulation of Vps4 by Ist1 corresponded with altered ESCRT-III disassembly in vitro. Together, these data support a model in which Ist1-Did2 interactions during ESCRT-III polymerization coordinate Vps4 activity with the timing of ESCRT-III disassembly.
AB - Intralumenal vesicle formation of the multivesicular body is a critical step in the delivery of endocytic cargoes to the lysosome for degradation. Endosomal sorting complex required for transport III (ESCRT-III) subunits polymerize on endosomal membranes to facilitate membrane budding away from the cytoplasm to generate these intralumenal vesicles. The ATPase Vps4 remodels and disassembles ESCRT-III, but the manner in which Vps4 activity is coordinated with ESCRT-III function remains unclear. Ist1 is structurally homologous to ESCRT-III subunits and has been reported to inhibit Vps4 function despite the presence of a microtubule-interacting and trafficking domain-interacting motif (MIM) capable of stimulating Vps4 in the context of other ESCRT-III subunits. Here we report that Ist1 inhibition of Vps4 ATPase activity involves two elements in Ist1: the MIM itself and a surface containing a conserved ELYC sequence. In contrast, the MI Minteraction, in concert with a more open conformation of the Ist1 core, resulted in stimulation of Vps4. Addition of the ESCRT-III subunit binding partner of Ist1, Did2, also converted Ist1 from an inhibitor to a stimulator of Vps4 ATPase activity. Finally, distinct regulation of Vps4 by Ist1 corresponded with altered ESCRT-III disassembly in vitro. Together, these data support a model in which Ist1-Did2 interactions during ESCRT-III polymerization coordinate Vps4 activity with the timing of ESCRT-III disassembly.
U2 - 10.1074/jbc.M115.665604
DO - 10.1074/jbc.M115.665604