EC Number |
General Information |
Reference |
---|
7.4.2.3 | malfunction |
temperature-sensitive mutants of mitochondrial Hsp70, affected in either ATP-binding and hydrolysis or Tim44 interaction, display defects in matrix protein import and concomitant TOM/TIM23-supercomplex formation when import reactions were performed under non-permissive conditions |
734764 |
7.4.2.3 | metabolism |
for the ATP-dependent translocation of preproteins into the aqueous matrix, TIM23CORE cooperates with the presequence translocase-associated import motor (PAM) that is composed of mitochondrial heat shock protein 70 (mtHsp70) and five co-chaperones that differentially regulate the import-driving ATPase activity of mtHsp70 and the assembly status of PAM: Tim44, Pam16, Pam17, Pam18, and Mge1. The biogenesis of presequence-carrying polytopic inner membrane proteins requires a close cooperation of the TIM23/PAM machinery with the export translocase Oxa1. Therefore, the TIM23 complex acts as an intricate multipurpose molecular machine in which the coupling of distinct partner proteins to TIM23CORE generates functional specificity |
734275 |
7.4.2.3 | more |
quantitative analysis of mitochondrial protein complexes, overview |
734275 |
7.4.2.3 | physiological function |
in mitochondria, matrix translocation of polypeptides depends on the ATP-powered mitochondrial Hsp70 (mtHsp70), the catalytic constituent of the presequence translocase-associated motor (PAM), at the trans side of the protein-conducting channel. mtHsp70 exists in a soluble pool mediating matrix protein folding and a TIM23-associated pool generating precursor velocity over the inner membrane. During precursor transport, a translocation intermediate is established in which the motor-associated, unfolded precursor simultaneously spans the TOM and TIM23 complexes thereby generating a mitochondrial contact site. For both activities, the soluble co-chaperone Mge1 stimulates ADP/ATP exchange. To drive precursor translocation, the Hsp70-import motor associates with the protein-conducting channel of the TIM23 complex, the ATPase cycle of Hsp70 is regulated in the context of a translocating polypeptide chain. The presence of all Hsp70 co-chaperones at the import channel is not sufficient to promote matrix protein import, instead a recharging of the active translocase with Pam18 is required for motor activity. Thus, a replenishment cycle of co-chaperones at the TIM23 complex is an integral part of Hsp70s ATPase cycle at the channel exit site and essential to maintain motor-driven mitochondrial protein import. The association of the membrane-bound co-chaperones with the Tim23 channel unit is a prerequisite for the spatially controlled mtHsp70 regulation in mitochondria. Pam18 needs to be recharged at the translocase in order to maintain progressive mtHsp70 activity, such a replenishment cycle of the translocases co-chaperone Pam18 drives the ATP hydrolysis of the import motor in the precursor-occupied translocase and thus precursor transport along the presequence pathway, overview |
734764 |
7.4.2.3 | physiological function |
the protein transports heat shock protein 70 into the nucleus to protect cellular homeostasis against heat shock |
751766 |