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High affinity binding between Hsp70 and the C‐terminal domain of the measles virus nucleoprotein requires an Hsp40 co‐chaperone
Author(s) -
Couturier Marie,
Buccellato Matt,
Costanzo Stéphanie,
Bourhis JeanMarie,
Shu Yaoling,
Nicaise Magali,
Desmadril Michel,
Flaudrops Christophe,
Longhi Sonia,
Oglesbee Michael
Publication year - 2009
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.982
Subject(s) - hsp70 , chaperone (clinical) , nucleoprotein , atp hydrolysis , biology , heat shock protein , nuclease , microbiology and biotechnology , nucleotide , atpase , chemistry , biophysics , biochemistry , virology , virus , enzyme , gene , medicine , pathology
The major inducible 70 kDa heat shock protein (hsp70) binds the measles virus (MeV) nucleocapsid with high affinity in an ATP‐dependent manner, stimulating viral transcription and genome replication, and profoundly influencing virulence in mouse models of brain infection. Binding is mediated by two hydrophobic motifs (Box‐2 and Box‐3) located within the C‐terminal domain (N TAIL ) of the nucleocapsid protein, with N TAIL being an intrinsically disordered domain. The current work showed that high affinity hsp70 binding to N TAIL requires an hsp40 co‐chaperone that interacts primarily with the hsp70 nucleotide binding domain (NBD) and displays no significant affinity for N TAIL . Hsp40 directly enhanced hsp70 ATPase activity in an N TAIL ‐dependent manner, and formation of hsp40–hsp70–N TAIL intracellular complexes required the presence of N TAIL Box‐2 and 3. Results are consistent with the functional interplay between hsp70 nucleotide and substrate binding domains (SBD), where ATP hydrolysis is rate limiting to high affinity binding to client proteins and is enhanced by hsp40. As such, hsp40 is an essential variable in understanding the outcome of MeV–hsp70 interactions. Copyright © 2009 John Wiley & Sons, Ltd.