RWD domain: a recurring module in kinetochore architecture shown by a Ctf19-Mcm21 complex structure.
The proteins Ctf19, Okp1, Mcm21 and Ame1 are the components of COMA, a subassembly of budding-yeast kinetochores. We have determined the crystal structure of a conserved COMA subcomplex--the Ctf19-Mcm21 heterodimer--from Kluyveromyces lactis. Both proteins contain 'double-RWD' domains, which together form a Y-shaped framework with flexible N-terminal extensions. The kinetochore proteins Csm1, Spc24 and Spc25 have related single RWD domains, and Ctf19 and Mcm21 associate with pseudo-twofold symmetry analogous to that in the Csm1 homodimer and the Spc24-Spc25 heterodimer. The double-RWD domain core of the Ctf19-Mcm21 heterodimer is sufficient for association with Okp1-Ame1; the less conserved N-terminal regions may interact with components of a more extensive 'CTF19 complex'. Our structure shows the RWD domain to be a recurring module of kinetochore architecture that may be present in other kinetochore substructures. Like many eukaryotic molecular machines, kinetochores may have evolved from simpler assemblies by multiplication of a few ancestral modules.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, Massachusetts 02115, USA.
Florian
F
Schmitzberger
Stephen C
SC
Harrison
D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry*; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins / Q000737:chemistry*; D005656:Fungal Proteins / Q000737:chemistry; D018386:Kinetochores / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D004718:Saccharomycetales / Q000737:chemistry / Q000378:metabolism
D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D005656:Fungal Proteins