Abstract：
:The exchange of metabolites between the mitochondrial matrix and the cytosol depends on β-barrel channels in the outer membrane and α-helical carrier proteins in the inner membrane. The essential translocase of the inner membrane (TIM) chaperones escort these proteins through the intermembrane space, but the structural and mechanistic details remain elusive. We have used an integrated structural biology approach to reveal the functional principle of TIM chaperones. Multiple clamp-like binding sites hold the mitochondrial membrane proteins in a translocation-competent elongated form, thus mimicking characteristics of co-translational membrane insertion. The bound preprotein undergoes conformational dynamics within the chaperone binding clefts, pointing to a multitude of dynamic local binding events. Mutations in these binding sites cause cell death or growth defects associated with impairment of carrier and β-barrel protein biogenesis. Our work reveals how a single mitochondrial "transfer-chaperone" system is able to guide α-helical and β-barrel membrane proteins in a "nascent chain-like" conformation through a ribosome-free compartment.
journal_name
Celljournal_title
Cellauthors
Weinhäupl K,Lindau C,Hessel A,Wang Y,Schütze C,Jores T,Melchionda L,Schönfisch B,Kalbacher H,Bersch B,Rapaport D,Brennich M,Lindorff-Larsen K,Wiedemann N,Schanda Pdoi
10.1016/j.cell.2018.10.039subject
Has Abstractpub_date
2018-11-15 00:00:00pages
1365-1379.e25issue
5eissn
0092-8674issn
1097-4172pii
S0092-8674(18)31395-3journal_volume
175pub_type
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