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The interaction of the mitochondrial protein importer TOMM34 with HSP70 is regulated by TOMM34 phosphorylation and binding to 14-3-3 adaptors

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F20%3A00536719" target="_blank" >RIV/61388971:_____/20:00536719 - isvavai.cz</a>

  • Alternative codes found

    RIV/00209805:_____/20:00078403 RIV/00216208:11310/20:10413574

  • Result on the web

    <a href="https://www.jbc.org/content/early/2020/05/05/jbc.RA120.012624.short" target="_blank" >https://www.jbc.org/content/early/2020/05/05/jbc.RA120.012624.short</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1074/jbc.RA120.012624" target="_blank" >10.1074/jbc.RA120.012624</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    The interaction of the mitochondrial protein importer TOMM34 with HSP70 is regulated by TOMM34 phosphorylation and binding to 14-3-3 adaptors

  • Original language description

    Translocase of outer mitochondrial membrane 34 (TOMM34) orchestrates heat shock protein 70 (HSP70)/HSP90?mediated transport of mitochondrial precursor proteins. Here, usingin vitrophosphorylation and refolding assays, analytical size-exclusion chromatography, and hydrogen/deuterium exchange MS, we found that TOMM34 associates with 14-3-3 proteins after its phosphorylation by protein kinase A (PKA). PKA preferentially targeted two serine residues in TOMM34: Ser(93)and Ser(160), located in the tetratricopeptide repeat 1 (TPR1) domain and the interdomain linker, respectively. Both of these residues were necessary for efficient 14-3-3 protein binding. We determined that phosphorylation-induced structural changes in TOMM34 are further augmented by binding to 14-3-3, leading to destabilization of TOMM34's secondary structure. We also observed that this interaction with 14-3-3 occludes the TOMM34 interaction interface with ATP-bound HSP70 dimers, which leaves them intact and thereby eliminates an inhibitory effect of TOMM34 on HSP70-mediated refoldingin vitro. In contrast, we noted that TOMM34 in complex with 14-3-3 could bind HSP90. Both TOMM34 and 14-3-3 participated in cytosolic precursor protein transport mediated by the coordinated activities of HSP70 and HSP90. Our results provide important insights into how PKA-mediated phosphorylation and 14-3-3 binding regulate the availability of TOMM34 for its interaction with HSP70.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2020

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Journal of Biological Chemistry

  • ISSN

    0021-9258

  • e-ISSN

  • Volume of the periodical

    295

  • Issue of the periodical within the volume

    27

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    17

  • Pages from-to

    8928-8944

  • UT code for WoS article

    000550698000005

  • EID of the result in the Scopus database

    2-s2.0-85087473503