Liu, Y and Gierasch, LM and Bahar, I
(2010)
Role of Hsp70 ATPase domain intrinsic dynamics and sequence evolution in enabling its functional interactions with NEFs.
PLoS Computational Biology, 6 (9).
ISSN 1553-734X
Abstract
Catalysis of ADP-ATP exchange by nucleotide exchange factors (NEFs) is central to the activity of Hsp70 molecular chaperones. Yet, the mechanism of interaction of this family of chaperones with NEFs is not well understood in the context of the sequence evolution and structural dynamics of Hsp70 ATPase domains. We studied the interactions of Hsp70 ATPase domains with four different NEFs on the basis of the evolutionary trace and co-evolution of the ATPase domain sequence, combined with elastic network modeling of the collective dynamics of the complexes. Our study reveals a subtle balance between the intrinsic (to the ATPase domain) and specific (to interactions with NEFs) mechanisms shared by the four complexes. Two classes of key residues are distinguished in the Hsp70 ATPase domain: (i) highly conserved residues, involved in nucleotide binding, which mediate, via a global hinge-bending, the ATPase domain opening irrespective of NEF binding, and (ii) not-conserved but co-evolved and highly mobile residues, engaged in specific interactions with NEFs (e.g., N57, R258, R262, E283, D285). The observed interplay between these respective intrinsic (pre-existing, structure-encoded) and specific (co-evolved, sequence-dependent) interactions provides us with insights into the allosteric dynamics and functional evolution of the modular Hsp70 ATPase domain. © 2010 Liu et al.
Share
Citation/Export: |
|
Social Networking: |
|
Details
Item Type: |
Article
|
Status: |
Published |
Creators/Authors: |
|
Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID  |
---|
Editor | Rost, Burkhard | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
|
Date: |
1 September 2010 |
Date Type: |
Publication |
Journal or Publication Title: |
PLoS Computational Biology |
Volume: |
6 |
Number: |
9 |
DOI or Unique Handle: |
10.1371/journal.pcbi.1000931 |
Schools and Programs: |
School of Medicine > Computational Biology |
Refereed: |
Yes |
ISSN: |
1553-734X |
MeSH Headings: |
Adenosine Triphosphatases--chemistry; Adenosine Triphosphatases--genetics; Adenosine Triphosphatases--metabolism; Amino Acid Sequence; Animals; Binding Sites; Cattle; Computational Biology; Escherichia coli Proteins--chemistry; Escherichia coli Proteins--genetics; Escherichia coli Proteins--metabolism; Evolution, Molecular; HSP70 Heat-Shock Proteins--chemistry; HSP70 Heat-Shock Proteins--genetics; HSP70 Heat-Shock Proteins--metabolism; Humans; Molecular Chaperones--chemistry; Molecular Chaperones--genetics; Molecular Chaperones--metabolism; Molecular Dynamics Simulation; Multiprotein Complexes; Normal Distribution; Phylogeny; Protein Structure, Tertiary; Sequence Alignment |
Other ID: |
NLM PMC2940730 |
PubMed Central ID: |
PMC2940730 |
PubMed ID: |
20862304 |
Date Deposited: |
15 Aug 2012 17:55 |
Last Modified: |
17 Mar 2023 11:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/13551 |
Metrics
Monthly Views for the past 3 years
Plum Analytics
Altmetric.com
Actions (login required)
 |
View Item |