Cargando…

The Link That Binds: The Linker of Hsp70 as a Helm of the Protein’s Function

The heat shock 70 (Hsp70) family of molecular chaperones plays a central role in maintaining cellular proteostasis. Structurally, Hsp70s are composed of an N-terminal nucleotide binding domain (NBD) which exhibits ATPase activity, and a C-terminal substrate binding domain (SBD). The binding of ATP a...

Descripción completa

Detalles Bibliográficos
Autores principales: Chakafana, Graham, Zininga, Tawanda, Shonhai, Addmore
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843406/
https://www.ncbi.nlm.nih.gov/pubmed/31569820
http://dx.doi.org/10.3390/biom9100543
_version_ 1783468207858778112
author Chakafana, Graham
Zininga, Tawanda
Shonhai, Addmore
author_facet Chakafana, Graham
Zininga, Tawanda
Shonhai, Addmore
author_sort Chakafana, Graham
collection PubMed
description The heat shock 70 (Hsp70) family of molecular chaperones plays a central role in maintaining cellular proteostasis. Structurally, Hsp70s are composed of an N-terminal nucleotide binding domain (NBD) which exhibits ATPase activity, and a C-terminal substrate binding domain (SBD). The binding of ATP at the NBD and its subsequent hydrolysis influences the substrate binding affinity of the SBD through allostery. Similarly, peptide binding at the C-terminal SBD stimulates ATP hydrolysis by the N-terminal NBD. Interdomain communication between the NBD and SBD is facilitated by a conserved linker segment. Hsp70s form two main subgroups. Canonical Hsp70 members generally suppress protein aggregation and are also capable of refolding misfolded proteins. Hsp110 members are characterized by an extended lid segment and their function tends to be largely restricted to suppression of protein aggregation. In addition, the latter serve as nucleotide exchange factors (NEFs) of canonical Hsp70s. The linker of the Hsp110 family is less conserved compared to that of the canonical Hsp70 group. In addition, the linker plays a crucial role in defining the functional features of these two groups of Hsp70. Generally, the linker of Hsp70 is quite small and varies in size from seven to thirteen residues. Due to its small size, any sequence variation that Hsp70 exhibits in this motif has a major and unique influence on the function of the protein. Based on sequence data, we observed that canonical Hsp70s possess a linker that is distinct from similar segments present in Hsp110 proteins. In addition, Hsp110 linker motifs from various genera are distinct suggesting that their unique features regulate the flexibility with which the NBD and SBD of these proteins communicate via allostery. The Hsp70 linker modulates various structure-function features of Hsp70 such as its global conformation, affinity for peptide substrate and interaction with co-chaperones. The current review discusses how the unique features of the Hsp70 linker accounts for the functional specialization of this group of molecular chaperones.
format Online
Article
Text
id pubmed-6843406
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-68434062019-11-25 The Link That Binds: The Linker of Hsp70 as a Helm of the Protein’s Function Chakafana, Graham Zininga, Tawanda Shonhai, Addmore Biomolecules Review The heat shock 70 (Hsp70) family of molecular chaperones plays a central role in maintaining cellular proteostasis. Structurally, Hsp70s are composed of an N-terminal nucleotide binding domain (NBD) which exhibits ATPase activity, and a C-terminal substrate binding domain (SBD). The binding of ATP at the NBD and its subsequent hydrolysis influences the substrate binding affinity of the SBD through allostery. Similarly, peptide binding at the C-terminal SBD stimulates ATP hydrolysis by the N-terminal NBD. Interdomain communication between the NBD and SBD is facilitated by a conserved linker segment. Hsp70s form two main subgroups. Canonical Hsp70 members generally suppress protein aggregation and are also capable of refolding misfolded proteins. Hsp110 members are characterized by an extended lid segment and their function tends to be largely restricted to suppression of protein aggregation. In addition, the latter serve as nucleotide exchange factors (NEFs) of canonical Hsp70s. The linker of the Hsp110 family is less conserved compared to that of the canonical Hsp70 group. In addition, the linker plays a crucial role in defining the functional features of these two groups of Hsp70. Generally, the linker of Hsp70 is quite small and varies in size from seven to thirteen residues. Due to its small size, any sequence variation that Hsp70 exhibits in this motif has a major and unique influence on the function of the protein. Based on sequence data, we observed that canonical Hsp70s possess a linker that is distinct from similar segments present in Hsp110 proteins. In addition, Hsp110 linker motifs from various genera are distinct suggesting that their unique features regulate the flexibility with which the NBD and SBD of these proteins communicate via allostery. The Hsp70 linker modulates various structure-function features of Hsp70 such as its global conformation, affinity for peptide substrate and interaction with co-chaperones. The current review discusses how the unique features of the Hsp70 linker accounts for the functional specialization of this group of molecular chaperones. MDPI 2019-09-27 /pmc/articles/PMC6843406/ /pubmed/31569820 http://dx.doi.org/10.3390/biom9100543 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Chakafana, Graham
Zininga, Tawanda
Shonhai, Addmore
The Link That Binds: The Linker of Hsp70 as a Helm of the Protein’s Function
title The Link That Binds: The Linker of Hsp70 as a Helm of the Protein’s Function
title_full The Link That Binds: The Linker of Hsp70 as a Helm of the Protein’s Function
title_fullStr The Link That Binds: The Linker of Hsp70 as a Helm of the Protein’s Function
title_full_unstemmed The Link That Binds: The Linker of Hsp70 as a Helm of the Protein’s Function
title_short The Link That Binds: The Linker of Hsp70 as a Helm of the Protein’s Function
title_sort link that binds: the linker of hsp70 as a helm of the protein’s function
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843406/
https://www.ncbi.nlm.nih.gov/pubmed/31569820
http://dx.doi.org/10.3390/biom9100543
work_keys_str_mv AT chakafanagraham thelinkthatbindsthelinkerofhsp70asahelmoftheproteinsfunction
AT ziningatawanda thelinkthatbindsthelinkerofhsp70asahelmoftheproteinsfunction
AT shonhaiaddmore thelinkthatbindsthelinkerofhsp70asahelmoftheproteinsfunction
AT chakafanagraham linkthatbindsthelinkerofhsp70asahelmoftheproteinsfunction
AT ziningatawanda linkthatbindsthelinkerofhsp70asahelmoftheproteinsfunction
AT shonhaiaddmore linkthatbindsthelinkerofhsp70asahelmoftheproteinsfunction