Structural details of an interaction between cardiolipin and an integral membrane protein

Abstract

Anionic lipids play a variety of key roles in biomembrane function, including providing the immediate environment for the integral membrane proteins that catalyze photosynthetic and respiratory energy transduction. Little is known about the molecular basis of these lipid-protein interactions. In this study, x-ray crystallography has been used to examine the structural details of an interaction between cardiolipin and the photoreaction center, a key lightdriven electron transfer protein complex found in the cytoplasmic membrane of photosynthetic bacteria. X-ray diffraction data collected over the resolution range 30.0 -2.1 Å show that binding of the lipid to the protein involves a combination of ionic interactions between the protein and the lipid headgroup and van der Waals interactions between the lipid tails and the electroneutral intramembrane surface of the protein. In the headgroup region, ionic interactions involve polar groups of a number of residues, the protein backbone, and bound water molecules. The lipid tails sit along largely hydrophobic grooves in the irregular surface of the protein. In addition to providing new information on the immediate lipid environment of a key integral membrane protein, this study provides the first, to our knowledge, high-resolution x-ray crystal structure for cardiolipin. The possible significance of this interaction between an integral membrane protein and cardiolipin is considered.

Interactions between lipids and bacterial reaction centers determined by protein crystallography

“…The overall structure of the protein is very similar to previous models of the RC from R. sphaeroides (5,8,(18)(19)(20), with no significant alterations of the cofactor organization or interactions between the cofactors and protein side chains. However, unlike previous models, the current model does include three bound lipids on the surface of the protein.…”

“…The electron density for the cardiolipin region was previously modeled as arising from a phosphate ion at the position of one of the phosphate moieties and a lauryl dimethylamine oxide molecule as discussed previously (5). More recently, the cardiolipin was identified in a nonfunctioning RC mutant (5). The other two lipids were not found presumably because the mutations caused significant structural changes involving the binding sites of the two lipids.…”

“…The rings of the lipid come within 4.5 Å of the esters of ring E and 5.5 Å to the conjugated macrocycle. The lipid chains make contact with the isoprenoid chain of Q A and Phe M258; this cofactor is lost and the region of the protein interacting with the fatty acid chain is significantly altered in the mutant structure of McAuley and coworkers (5). The phosphatidylcholine binds at the interface between the L and M subunits with the phosphate near the inactive bacteriopheophytin (Fig.…”

The action of cardiolipin on the bacterial translocon

“…Even after extensive purification, these enzymes retain bound CL, and complete delipidation consistently leads to the irreversible dissociation of their native oligomeric structures (33,34). Our results provide a comprehensive description of an active role for CL in Sec-dependent protein transport.…”

“…The role of CL has mostly been documented in relation to the preservation of optimal activity, stability, and supramolecular organization of bioenergetic enzymes such as the cytochrome bc1 complex (31), ATP synthase (32), cytochrome c oxidase (33), and the photoreaction center (34). Even after extensive purification, these enzymes retain bound CL, and complete delipidation consistently leads to the irreversible dissociation of their native oligomeric structures (33,34).…”