PMID- 17050688 OWN - NLM STAT- MEDLINE DCOM- 20061222 LR - 20181113 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 103 IP - 44 DP - 2006 Oct 31 TI - Identification of conserved lipid/detergent-binding sites in a high-resolution structure of the membrane protein cytochrome c oxidase. PG - 16117-22 AB - Well ordered reproducible crystals of cytochrome c oxidase (CcO) from Rhodobacter sphaeroides yield a previously unreported structure at 2.0 A resolution that contains the two catalytic subunits and a number of alkyl chains of lipids and detergents. Comparison with crystal structures of other bacterial and mammalian CcOs reveals that the positions occupied by native membrane lipids and detergent substitutes are highly conserved, along with amino acid residues in their vicinity, suggesting a more prevalent and specific role of lipid in membrane protein structure than often envisioned. Well defined detergent head groups (maltose) are found associated with aromatic residues in a manner similar to phospholipid head groups, likely contributing to the success of alkyl glycoside detergents in supporting membrane protein activity and crystallizability. Other significant features of this structure include the following: finding of a previously unreported crystal contact mediated by cadmium and an engineered histidine tag; documentation of the unique His-Tyr covalent linkage close to the active site; remarkable conservation of a chain of waters in one proton pathway (D-path); and discovery of an inhibitory cadmium-binding site at the entrance to another proton path (K-path). These observations provide important insight into CcO structure and mechanism, as well as the significance of bound lipid in membrane proteins. FAU - Qin, Ling AU - Qin L AD - Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. FAU - Hiser, Carrie AU - Hiser C FAU - Mulichak, Anne AU - Mulichak A FAU - Garavito, R Michael AU - Garavito RM FAU - Ferguson-Miller, Shelagh AU - Ferguson-Miller S LA - eng SI - PDB/2GSM GR - R01 GM026916/GM/NIGMS NIH HHS/United States GR - R37 GM026916/GM/NIGMS NIH HHS/United States GR - GM 26916/GM/NIGMS NIH HHS/United States GR - P01 GM 57323/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20061018 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Detergents) RN - 0 (Lipids) RN - 0 (Protein Subunits) RN - 0 (Protons) RN - 00BH33GNGH (Cadmium) RN - 059QF0KO0R (Water) RN - 42HK56048U (Tyrosine) RN - 4QD397987E (Histidine) RN - EC 1.9.3.1 (Electron Transport Complex IV) SB - IM MH - Binding Sites MH - Cadmium/chemistry/metabolism MH - Crystallization MH - Crystallography, X-Ray MH - Detergents/*chemistry/*metabolism MH - Electron Transport Complex IV/*chemistry/genetics/isolation & purification/*metabolism MH - Electrons MH - Histidine/chemistry/metabolism MH - *Lipid Metabolism MH - Lipids/*chemistry MH - Models, Molecular MH - Protein Engineering MH - Protein Structure, Quaternary MH - Protein Structure, Tertiary MH - Protein Subunits/chemistry/genetics/metabolism MH - Protons MH - Rhodobacter sphaeroides/enzymology/genetics MH - Tyrosine/chemistry/metabolism MH - Water/chemistry PMC - PMC1616942 COIS- The authors declare no conflict of interest. EDAT- 2006/10/20 09:00 MHDA- 2006/12/23 09:00 PMCR- 2006/10/31 CRDT- 2006/10/20 09:00 PHST- 2006/10/20 09:00 [pubmed] PHST- 2006/12/23 09:00 [medline] PHST- 2006/10/20 09:00 [entrez] PHST- 2006/10/31 00:00 [pmc-release] AID - 0606149103 [pii] AID - 3863 [pii] AID - 10.1073/pnas.0606149103 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16117-22. doi: 10.1073/pnas.0606149103. Epub 2006 Oct 18.