The Role of the Arginine in the Conserved N-Terminal Domain RLFDQxFG Motif of Human Small Heat Shock Proteins HspB1, HspB4, HspB5, HspB6, and HspB8
Although the N-terminal domain of vertebrate small heat shock proteins (sHsp) is poorly conserved, it contains a core motif preserved in many members of the sHsp family. The role of this RLFDQxFG motif remains elusive. We analyzed the specific role of the first arginine residue of this conserved oct...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2018-07-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | http://www.mdpi.com/1422-0067/19/7/2112 |
id |
doaj-b43e52ba75304aa99909aece0a3e5f83 |
---|---|
record_format |
Article |
spelling |
doaj-b43e52ba75304aa99909aece0a3e5f832020-11-25T00:34:55ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-07-01197211210.3390/ijms19072112ijms19072112The Role of the Arginine in the Conserved N-Terminal Domain RLFDQxFG Motif of Human Small Heat Shock Proteins HspB1, HspB4, HspB5, HspB6, and HspB8Vladislav M. Shatov0Stephen D. Weeks1Sergei V. Strelkov2Nikolai B. Gusev3Department of Biochemistry, School of Biology, Moscow State University, Moscow 119991, RussiaLaboratory of Biocrystallography, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven 3000, BelgiumLaboratory of Biocrystallography, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven 3000, BelgiumDepartment of Biochemistry, School of Biology, Moscow State University, Moscow 119991, RussiaAlthough the N-terminal domain of vertebrate small heat shock proteins (sHsp) is poorly conserved, it contains a core motif preserved in many members of the sHsp family. The role of this RLFDQxFG motif remains elusive. We analyzed the specific role of the first arginine residue of this conserved octet sequence in five human sHsps (HspB1, HspB4, HspB5, HspB6, and HspB8). Substitution of this arginine with an alanine induced changes in thermal stability and/or intrinsic fluorescence of the related HspB1 and HspB8, but yielded only modest changes in the same biophysical properties of HspB4, HspB5, and HspB6 which together belong to another clade of vertebrate sHsps. Removal of the positively charged Arg side chain resulted in destabilization of the large oligomers of HspB1 and formation of smaller size oligomers of HspB5. The mutation induced only minor changes in the structure of HspB4 and HspB6. In contrast, the mutation in HspB8 was accompanied by shifting the equilibrium from dimers towards the formation of larger oligomers. We conclude that the RLFDQxFG motif plays distinct roles in the structure of several sHsp orthologs. This role correlates with the evolutionary relationship of the respective sHsps, but ultimately, it reflects the sequence context of this motif.http://www.mdpi.com/1422-0067/19/7/2112small heat shock proteinsoligomer structurechaperone-like activitydisease-related mutations |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Vladislav M. Shatov Stephen D. Weeks Sergei V. Strelkov Nikolai B. Gusev |
spellingShingle |
Vladislav M. Shatov Stephen D. Weeks Sergei V. Strelkov Nikolai B. Gusev The Role of the Arginine in the Conserved N-Terminal Domain RLFDQxFG Motif of Human Small Heat Shock Proteins HspB1, HspB4, HspB5, HspB6, and HspB8 International Journal of Molecular Sciences small heat shock proteins oligomer structure chaperone-like activity disease-related mutations |
author_facet |
Vladislav M. Shatov Stephen D. Weeks Sergei V. Strelkov Nikolai B. Gusev |
author_sort |
Vladislav M. Shatov |
title |
The Role of the Arginine in the Conserved N-Terminal Domain RLFDQxFG Motif of Human Small Heat Shock Proteins HspB1, HspB4, HspB5, HspB6, and HspB8 |
title_short |
The Role of the Arginine in the Conserved N-Terminal Domain RLFDQxFG Motif of Human Small Heat Shock Proteins HspB1, HspB4, HspB5, HspB6, and HspB8 |
title_full |
The Role of the Arginine in the Conserved N-Terminal Domain RLFDQxFG Motif of Human Small Heat Shock Proteins HspB1, HspB4, HspB5, HspB6, and HspB8 |
title_fullStr |
The Role of the Arginine in the Conserved N-Terminal Domain RLFDQxFG Motif of Human Small Heat Shock Proteins HspB1, HspB4, HspB5, HspB6, and HspB8 |
title_full_unstemmed |
The Role of the Arginine in the Conserved N-Terminal Domain RLFDQxFG Motif of Human Small Heat Shock Proteins HspB1, HspB4, HspB5, HspB6, and HspB8 |
title_sort |
role of the arginine in the conserved n-terminal domain rlfdqxfg motif of human small heat shock proteins hspb1, hspb4, hspb5, hspb6, and hspb8 |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2018-07-01 |
description |
Although the N-terminal domain of vertebrate small heat shock proteins (sHsp) is poorly conserved, it contains a core motif preserved in many members of the sHsp family. The role of this RLFDQxFG motif remains elusive. We analyzed the specific role of the first arginine residue of this conserved octet sequence in five human sHsps (HspB1, HspB4, HspB5, HspB6, and HspB8). Substitution of this arginine with an alanine induced changes in thermal stability and/or intrinsic fluorescence of the related HspB1 and HspB8, but yielded only modest changes in the same biophysical properties of HspB4, HspB5, and HspB6 which together belong to another clade of vertebrate sHsps. Removal of the positively charged Arg side chain resulted in destabilization of the large oligomers of HspB1 and formation of smaller size oligomers of HspB5. The mutation induced only minor changes in the structure of HspB4 and HspB6. In contrast, the mutation in HspB8 was accompanied by shifting the equilibrium from dimers towards the formation of larger oligomers. We conclude that the RLFDQxFG motif plays distinct roles in the structure of several sHsp orthologs. This role correlates with the evolutionary relationship of the respective sHsps, but ultimately, it reflects the sequence context of this motif. |
topic |
small heat shock proteins oligomer structure chaperone-like activity disease-related mutations |
url |
http://www.mdpi.com/1422-0067/19/7/2112 |
work_keys_str_mv |
AT vladislavmshatov theroleofthearginineintheconservednterminaldomainrlfdqxfgmotifofhumansmallheatshockproteinshspb1hspb4hspb5hspb6andhspb8 AT stephendweeks theroleofthearginineintheconservednterminaldomainrlfdqxfgmotifofhumansmallheatshockproteinshspb1hspb4hspb5hspb6andhspb8 AT sergeivstrelkov theroleofthearginineintheconservednterminaldomainrlfdqxfgmotifofhumansmallheatshockproteinshspb1hspb4hspb5hspb6andhspb8 AT nikolaibgusev theroleofthearginineintheconservednterminaldomainrlfdqxfgmotifofhumansmallheatshockproteinshspb1hspb4hspb5hspb6andhspb8 AT vladislavmshatov roleofthearginineintheconservednterminaldomainrlfdqxfgmotifofhumansmallheatshockproteinshspb1hspb4hspb5hspb6andhspb8 AT stephendweeks roleofthearginineintheconservednterminaldomainrlfdqxfgmotifofhumansmallheatshockproteinshspb1hspb4hspb5hspb6andhspb8 AT sergeivstrelkov roleofthearginineintheconservednterminaldomainrlfdqxfgmotifofhumansmallheatshockproteinshspb1hspb4hspb5hspb6andhspb8 AT nikolaibgusev roleofthearginineintheconservednterminaldomainrlfdqxfgmotifofhumansmallheatshockproteinshspb1hspb4hspb5hspb6andhspb8 |
_version_ |
1725311457210400768 |