Structural basis of Sec-independent membrane protein insertion by YidC

• Published in: Nature (London) 2014-05, Vol.509 (7501), p.516-520
• Main Authors: Kumazaki, Kaoru, Chiba, Shinobu, Takemoto, Mizuki, Furukawa, Arata, Nishiyama, Ken-ichi, Sugano, Yasunori, Mori, Takaharu, Dohmae, Naoshi, Hirata, Kunio, Nakada-Nakura, Yoshiko, Maturana, Andrés D., Tanaka, Yoshiki, Mori, Hiroyuki, Sugita, Yuji, Arisaka, Fumio, Ito, Koreaki, Ishitani, Ryuichiro, Tsukazaki, Tomoya, Nureki, Osamu
• Format: Article
• Language: English
• Subjects: 631/535/1266; Arginine - metabolism; Bacillus - chemistry; Bacterial proteins; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Bacteriology; Cell Membrane - chemistry; Cell Membrane - metabolism; Conserved Sequence; Crystallography, X-Ray; Crystals; E coli; Humanities and Social Sciences; Hydrophobic and Hydrophilic Interactions; Hydrophobicity; letter; Lipids; Measurement; Membrane proteins; Membrane Transport Proteins - chemistry; Membrane Transport Proteins - metabolism; Membranes; Molecular Chaperones - chemistry; Molecular Chaperones - metabolism; Molecular structure; multidisciplinary; Observations; Physiological aspects; Properties; Protein Folding; Protein research; Proteins; Science; Static Electricity; Structure; Structure-Activity Relationship
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature13167

The crystal structure of the bacterial protein YidC is reported, together with a structure-based functional analysis, providing insight into the role of YidC in inserting single-spanning membrane proteins into the membrane. Structure of YidC from Bacillus halodurans The bacterial protein YidC, a homologue of mitochondrial Oxa1 and chloroplast Alb3, is not just a chaperone that facilitates proper folding and membrane topology of its membrane-protein substrates, in cooperation with the Sec machinery. It also inserts several single- or double-spanning membrane proteins into the membrane independently of Sec. Osamu Nureki and colleagues present the long-awaited structure of YidC, which provides insights into the second role of this membrane protein. The structure suggests that YidC does not adopt a polypeptide-conducting channel-like architecture. Instead, a novel fold within the protein forms a positively charged hydrophilic groove. The authors, using structure-based functional analysis, reveal that electrostatic interactions between a conserved Arg residue in the groove and the acidic residues at the N-terminal region of a substrate protein are essential for the YidC-mediated insertion of the substrate into the membrane. Newly synthesized membrane proteins must be accurately inserted into the membrane, folded and assembled for proper functioning. The protein YidC inserts its substrates into the membrane, thereby facilitating membrane protein assembly in bacteria; the homologous proteins Oxa1 and Alb3 have the same function in mitochondria and chloroplasts, respectively 1 , 2 . In the bacterial cytoplasmic membrane, YidC functions as an independent insertase and a membrane chaperone in cooperation with the translocon SecYEG 3 , 4 , 5 . Here we present the crystal structure of YidC from Bacillus halodurans , at 2.4 Å resolution. The structure reveals a novel fold, in which five conserved transmembrane helices form a positively charged hydrophilic groove that is open towards both the lipid bilayer and the cytoplasm but closed on the extracellular side. Structure-based in vivo analyses reveal that a conserved arginine residue in the groove is important for the insertion of membrane proteins by YidC. We propose an insertion mechanism for single-spanning membrane proteins, in which the hydrophilic environment generated by the groove recruits the extracellular regions of substrates into the low-dielectric environment of the membrane.