--- res: bibo_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.@eng bibo_authorlist: - foaf_Person: foaf_givenName: Katharina foaf_name: Weinhäupl, Katharina foaf_surname: Weinhäupl - foaf_Person: foaf_givenName: Caroline foaf_name: Lindau, Caroline foaf_surname: Lindau - foaf_Person: foaf_givenName: Audrey foaf_name: Hessel, Audrey foaf_surname: Hessel - foaf_Person: foaf_givenName: Yong foaf_name: Wang, Yong foaf_surname: Wang - foaf_Person: foaf_givenName: Conny foaf_name: Schütze, Conny foaf_surname: Schütze - foaf_Person: foaf_givenName: Tobias foaf_name: Jores, Tobias foaf_surname: Jores - foaf_Person: foaf_givenName: Laura foaf_name: Melchionda, Laura foaf_surname: Melchionda - foaf_Person: foaf_givenName: Birgit foaf_name: Schönfisch, Birgit foaf_surname: Schönfisch - foaf_Person: foaf_givenName: Hubert foaf_name: Kalbacher, Hubert foaf_surname: Kalbacher - foaf_Person: foaf_givenName: Beate foaf_name: Bersch, Beate foaf_surname: Bersch - foaf_Person: foaf_givenName: Doron foaf_name: Rapaport, Doron foaf_surname: Rapaport - foaf_Person: foaf_givenName: Martha foaf_name: Brennich, Martha foaf_surname: Brennich - foaf_Person: foaf_givenName: Kresten foaf_name: Lindorff-Larsen, Kresten foaf_surname: Lindorff-Larsen - foaf_Person: foaf_givenName: Nils foaf_name: Wiedemann, Nils foaf_surname: Wiedemann - foaf_Person: foaf_givenName: Paul foaf_name: Schanda, Paul foaf_surname: Schanda foaf_workInfoHomepage: http://www.librecat.org/personId=7B541462-FAF6-11E9-A490-E8DFE5697425 orcid: 0000-0002-9350-7606 bibo_doi: 10.1016/j.cell.2018.10.039 bibo_issue: '5' bibo_volume: 175 dct_date: 2018^xs_gYear dct_isPartOf: - http://id.crossref.org/issn/0092-8674 dct_language: eng dct_publisher: Elsevier@ dct_subject: - General Biochemistry - Genetics and Molecular Biology dct_title: Structural basis of membrane protein chaperoning through the mitochondrial intermembrane space@ ...