Computational Advances in Structural Biology

Abstract

The electron transport chain involves four protein complexes (CI-IV) that reside in the inner mitochondrial membrane, using the energy from redox reactions to establish an electrochemical proton gradient used for ATP production. Recent biological studies, especially using single-particle cryo-EM analysis, have revealed several different types of supramolecular organizations of these enzymes. In our research, we found two new types of respiratory supercomplexes, CIICIII2CIV(1/2), in Perkinsus marinus. Furthermore, we observed two previously unknown extra proteins (named ISPR1/2) binding to the cytochrome c binding site at complex III (CIII) and interacting with Rieske iron-sulfur protein (ISP) during the c1-state of ISP, indicating a unique mechanism of electron transfer. Our structure provides strong evidence for the existence of CII in a supercomplex and reveals frameshifting in all three protein-coding genes in the mitochondria. The unique arrangement of CII, CIII, and CIV in the supercomplex reveals a specific adaptation in the electron transfer chain of P. marinus and the discovered interaction between CIII and ISPR1/2 suggests a novel regulatory mechanism in oxidative phosphorylation.