title: Structural basis for tail-anchored membrane protein biogenesis by the Get3-receptor complex.
abstract: Tail-anchored (TA) proteins are involved in cellular processes including trafficking, degradation, and apoptosis. They contain a C-terminal membrane anchor and are posttranslationally delivered to the endoplasmic reticulum (ER) membrane by the Get3 adenosine triphosphatase interacting with the hetero-oligomeric Get1/2 receptor. We have determined crystal structures of Get3 in complex with the cytosolic domains of Get1 and Get2 in different functional states at 3.0, 3.2, and 4.6 angstrom resolution. The structural data, together with biochemical experiments, show that Get1 and Get2 use adjacent, partially overlapping binding sites and that both can bind simultaneously to Get3. Docking to the Get1/2 complex allows for conformational changes in Get3 that are required for TA protein insertion. These data suggest a molecular mechanism for nucleotide-regulated delivery of TA proteins.
authors: Institute for Biophysical Chemistry, Centre for Biomolecular Magnetic Resonance, Goethe University, D-60325 Frankfurt am Main, Germany.
authors: Susanne
authors: S
authors: Stefer
authors: Simon
authors: S
authors: Reitz
authors: Fei
authors: F
authors: Wang
authors: Klemens
authors: K
authors: Wild
authors: Yin-Yuin
authors: YY
authors: Pang
authors: Daniel
authors: D
authors: Schwarz
authors: Jörg
authors: J
authors: Bomke
authors: Christopher
authors: C
authors: Hein
authors: Frank
authors: F
authors: Löhr
authors: Frank
authors: F
authors: Bernhard
authors: Vladimir
authors: V
authors: Denic
authors: Volker
authors: V
authors: Dötsch
authors: Irmgard
authors: I
authors: Sinning
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry* / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003600:Cytosol / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry* / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C503510:GET1 protein, S cerevisiae; C515526:Get2 protein, S cerevisiae; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C529048:Get3 protein, S cerevisiae