Structure of the Hsp110:Hsc70 Nucleotide Exchange Machine

Jonathan P. Schuermann; Jianwen Jiang; Jorge Cuellar; Oscar Llorca; Liping Wang; Luis E. Gimenez; Suping Jin; Alexander B. Taylor; Borries Demeler; Kevin A. Morano; P. John Hart; Jose M. Valpuesta; Eileen M. Lafer; Rui Sousa

doi:10.1016/j.molcel.2008.05.006

Structure of the Hsp110:Hsc70 Nucleotide Exchange Machine

Jonathan P. Schuermann, Jianwen Jiang, Jorge Cuellar, Oscar Llorca, Liping Wang, Luis E. Gimenez, Suping Jin, Alexander B. Taylor, Borries Demeler, Kevin A. Morano, P. John Hart, Jose M. Valpuesta, Eileen M. Lafer, Rui Sousa

Chemistry and Biochemistry

Research output: Contribution to journal › Article › peer-review

197 Scopus citations

Abstract

Hsp70s mediate protein folding, translocation, and macromolecular complex remodeling reactions. Their activities are regulated by proteins that exchange ADP for ATP from the nucleotide-binding domain (NBD) of the Hsp70. These nucleotide exchange factors (NEFs) include the Hsp110s, which are themselves members of the Hsp70 family. We report the structure of an Hsp110:Hsc70 nucleotide exchange complex. The complex is characterized by extensive protein:protein interactions and symmetric bridging interactions between the nucleotides bound in each partner protein's NBD. An electropositive pore allows nucleotides to enter and exit the complex. The role of nucleotides in complex formation and dissociation, and the effects of the protein:protein interactions on nucleotide exchange, can be understood in terms of the coupled effects of the nucleotides and protein:protein interactions on the open-closed isomerization of the NBDs. The symmetrical interactions in the complex may model other Hsp70 family heterodimers in which two Hsp70s reciprocally act as NEFs.

Original language	English
Pages (from-to)	232-243
Number of pages	12
Journal	Molecular Cell
Volume	31
Issue number	2
DOIs	https://doi.org/10.1016/j.molcel.2008.05.006
State	Published - Jul 25 2008

Funding

Supported by GM-52522, AQ-1486, and 0755057Y from the NIH, Welch Foundation, and AHA, respectively (to R.S.); NS029051 from NINDS (to E.M.L.); NIH T32AG021890-03 (to J.P.S.); AQ-1399 from the Welch Foundation (to P.J.H.); BFU2007-62382/BMC from MEC and the EU-grant “3D repertoire” (LSHG-CT-2005-512028) (to J.M.V.); and SAF2005-00775 from MEC (O.L.). Support for the X-ray Crystallography, Mass Spectroscopy, and UTHSCSA Center for Macromolecular Interaction cores from the UTHSCSA ERC and SACI (5P30CA5174) is acknowledged. We thank Jay C. Nix and Virgil Schirf for, respectively, X-ray and AUC data collection. To mark his becoming Emeritus, this paper is dedicated to Merle Olson, who had the vision of developing a structural biology program in San Antonio.

Funders	Funder number
T32AG021890
BFU2007-62382/BMC, AQ-1399
American Heart Association	NS029051
SAF2005-00775, LSHG-CT-2005-512028

Keywords

PROTEINS

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10.1016/j.molcel.2008.05.006

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title = "Structure of the Hsp110:Hsc70 Nucleotide Exchange Machine",

abstract = "Hsp70s mediate protein folding, translocation, and macromolecular complex remodeling reactions. Their activities are regulated by proteins that exchange ADP for ATP from the nucleotide-binding domain (NBD) of the Hsp70. These nucleotide exchange factors (NEFs) include the Hsp110s, which are themselves members of the Hsp70 family. We report the structure of an Hsp110:Hsc70 nucleotide exchange complex. The complex is characterized by extensive protein:protein interactions and symmetric bridging interactions between the nucleotides bound in each partner protein's NBD. An electropositive pore allows nucleotides to enter and exit the complex. The role of nucleotides in complex formation and dissociation, and the effects of the protein:protein interactions on nucleotide exchange, can be understood in terms of the coupled effects of the nucleotides and protein:protein interactions on the open-closed isomerization of the NBDs. The symmetrical interactions in the complex may model other Hsp70 family heterodimers in which two Hsp70s reciprocally act as NEFs.",

keywords = "PROTEINS",

author = "Schuermann, \{Jonathan P.\} and Jianwen Jiang and Jorge Cuellar and Oscar Llorca and Liping Wang and Gimenez, \{Luis E.\} and Suping Jin and Taylor, \{Alexander B.\} and Borries Demeler and Morano, \{Kevin A.\} and Hart, \{P. John\} and Valpuesta, \{Jose M.\} and Lafer, \{Eileen M.\} and Rui Sousa",

note = "Funding Information: Supported by GM-52522, AQ-1486, and 0755057Y from the NIH, Welch Foundation, and AHA, respectively (to R.S.); NS029051 from NINDS (to E.M.L.); NIH T32AG021890-03 (to J.P.S.); AQ-1399 from the Welch Foundation (to P.J.H.); BFU2007-62382/BMC from MEC and the EU-grant “3D repertoire” (LSHG-CT-2005-512028) (to J.M.V.); and SAF2005-00775 from MEC (O.L.). Support for the X-ray Crystallography, Mass Spectroscopy, and UTHSCSA Center for Macromolecular Interaction cores from the UTHSCSA ERC and SACI (5P30CA5174) is acknowledged. We thank Jay C. Nix and Virgil Schirf for, respectively, X-ray and AUC data collection. To mark his becoming Emeritus, this paper is dedicated to Merle Olson, who had the vision of developing a structural biology program in San Antonio. ",

year = "2008",

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doi = "10.1016/j.molcel.2008.05.006",

language = "English",

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T1 - Structure of the Hsp110:Hsc70 Nucleotide Exchange Machine

AU - Schuermann, Jonathan P.

AU - Jiang, Jianwen

AU - Cuellar, Jorge

AU - Llorca, Oscar

AU - Wang, Liping

AU - Gimenez, Luis E.

AU - Jin, Suping

AU - Taylor, Alexander B.

AU - Demeler, Borries

AU - Morano, Kevin A.

AU - Hart, P. John

AU - Valpuesta, Jose M.

AU - Lafer, Eileen M.

AU - Sousa, Rui

N1 - Funding Information: Supported by GM-52522, AQ-1486, and 0755057Y from the NIH, Welch Foundation, and AHA, respectively (to R.S.); NS029051 from NINDS (to E.M.L.); NIH T32AG021890-03 (to J.P.S.); AQ-1399 from the Welch Foundation (to P.J.H.); BFU2007-62382/BMC from MEC and the EU-grant “3D repertoire” (LSHG-CT-2005-512028) (to J.M.V.); and SAF2005-00775 from MEC (O.L.). Support for the X-ray Crystallography, Mass Spectroscopy, and UTHSCSA Center for Macromolecular Interaction cores from the UTHSCSA ERC and SACI (5P30CA5174) is acknowledged. We thank Jay C. Nix and Virgil Schirf for, respectively, X-ray and AUC data collection. To mark his becoming Emeritus, this paper is dedicated to Merle Olson, who had the vision of developing a structural biology program in San Antonio.

PY - 2008/7/25

Y1 - 2008/7/25

N2 - Hsp70s mediate protein folding, translocation, and macromolecular complex remodeling reactions. Their activities are regulated by proteins that exchange ADP for ATP from the nucleotide-binding domain (NBD) of the Hsp70. These nucleotide exchange factors (NEFs) include the Hsp110s, which are themselves members of the Hsp70 family. We report the structure of an Hsp110:Hsc70 nucleotide exchange complex. The complex is characterized by extensive protein:protein interactions and symmetric bridging interactions between the nucleotides bound in each partner protein's NBD. An electropositive pore allows nucleotides to enter and exit the complex. The role of nucleotides in complex formation and dissociation, and the effects of the protein:protein interactions on nucleotide exchange, can be understood in terms of the coupled effects of the nucleotides and protein:protein interactions on the open-closed isomerization of the NBDs. The symmetrical interactions in the complex may model other Hsp70 family heterodimers in which two Hsp70s reciprocally act as NEFs.

AB - Hsp70s mediate protein folding, translocation, and macromolecular complex remodeling reactions. Their activities are regulated by proteins that exchange ADP for ATP from the nucleotide-binding domain (NBD) of the Hsp70. These nucleotide exchange factors (NEFs) include the Hsp110s, which are themselves members of the Hsp70 family. We report the structure of an Hsp110:Hsc70 nucleotide exchange complex. The complex is characterized by extensive protein:protein interactions and symmetric bridging interactions between the nucleotides bound in each partner protein's NBD. An electropositive pore allows nucleotides to enter and exit the complex. The role of nucleotides in complex formation and dissociation, and the effects of the protein:protein interactions on nucleotide exchange, can be understood in terms of the coupled effects of the nucleotides and protein:protein interactions on the open-closed isomerization of the NBDs. The symmetrical interactions in the complex may model other Hsp70 family heterodimers in which two Hsp70s reciprocally act as NEFs.

KW - PROTEINS

UR - https://www.scopus.com/pages/publications/45849091944

U2 - 10.1016/j.molcel.2008.05.006

DO - 10.1016/j.molcel.2008.05.006

M3 - Article

C2 - 18550409

AN - SCOPUS:45849091944

SN - 1097-2765

VL - 31

SP - 232

EP - 243

JO - Molecular Cell

JF - Molecular Cell

IS - 2

ER -

Structure of the Hsp110:Hsc70 Nucleotide Exchange Machine

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