Electrostatic funneling of substrate in mitochondrial inner membrane carriers.

ABSTRACT: Exchange of ATP and ADP across mitochondrial membrane replenishes the cytoplasm with newly synthesized ATP and provides the mitochondria with the substrate ADP for oxidative phosphorylation. The sole means of this exchange is the mitochondrial ADP/ATP carrier (AAC), a membrane protein that is suggested to cycle between two conformationally distinct states, cytosolic-open (c-state) and matrix-open (m-state), thereby shuttling nucleotides across the inner mitochondrial membrane. However, the c-state is the only structurally resolved state, and the binding site of ADP remains elusive. Here, we present approximately 0.3 mus of all-atom MD simulations of the c-state revealing rapid, spontaneous binding of ADP to deeply positioned binding sites within the AAC lumen. To our knowledge, a complete

SUBMITTER: Wang Y 

PROVIDER: S-EPMC2474497 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature