Structure-based assembly of protein complexes in yeast.
Images of entire cells are preceding atomic structures of the separate molecular machines that they contain. The resulting gap in knowledge can be partly bridged by protein-protein interactions, bioinformatics, and electron microscopy. Here we use interactions of known three-dimensional structure to model a large set of yeast complexes, which we also screen by electron microscopy. For 54 of 102 complexes, we obtain at least partial models of interacting subunits. For 29, including the exosome, the chaperonin containing TCP-1, a 3'-messenger RNA degradation complex, and RNA polymerase II, the process suggests atomic details not easily seen by homology, involving the combination of two or more known structures. We also consider interactions between complexes (cross-talk) and use these to construct a structure-based network of molecular machines in the cell.
Aloy
Patrick
P
European Molecular Biology Laboratory, Structural and Computational Biology Programme, 1, 69117 Heidelberg, Germany.
Böttcher
Bettina
B
Ceulemans
Hugo
H
Leutwein
Christina
C
Mellwig
Christian
C
Fischer
Susanne
S
Gavin
Anne-Claude
AC
Bork
Peer
P
Superti-Furga
Giulio
G
Serrano
Luis
L
Russell
Robert B
RB
D018833:Chaperonins / Q000737:chemistry / Q000378:metabolism; D019295:Computational Biology; D007091:Image Processing, Computer-Assisted; D008854:Microscopy, Electron; D008954:Models, Biological; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000737:chemistry / Q000378:metabolism; D043262:Ribonuclease P / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
D009687:Nuclear Proteins; C081929:SKI2 protein, S cerevisiae; C406671:SKI3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D012319:RNA Polymerase II; D043262:Ribonuclease P; D018833:Chaperonins