ABSTRACT
Kinetochores are the elaborate protein assemblies that attach chromosomes to spindle microtubules in mitosis and meiosis. The kinetochores of point-centromere yeast appear to represent an elementary module, which repeats a number of times in kinetochores assembled on regional centromeres. Structural analyses of the discrete protein subcomplexes that make up the budding-yeast kinetochore have begun to reveal principles of kinetochore architecture and to uncover molecular mechanisms underlying functions such as transmission of tension and establishment and maintenance of bipolar attachment. The centromeric DNA is probably wrapped into a compact organization, not only by a conserved, centromeric nucleosome, but also by interactions among various other DNA-bound kinetochore components. The rod-like, heterotetrameric Ndc80 complex, roughly 600 Å long, appears to extend from the DNA-proximal assembly to the plus end of a microtubule, to which one end of the complex is known to bind. Ongoing structural studies will clarify the roles of a number of other well-defined complexes.
Subject(s)
Kinetochores/chemistry , Kinetochores/metabolism , Saccharomyces cerevisiae Proteins/chemistry , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Kinetochores/ultrastructure , Microtubules/metabolism , Models, Biological , Multiprotein Complexes/chemistry , Multiprotein Complexes/metabolism , Multiprotein Complexes/ultrastructure , Protein Binding , Saccharomyces cerevisiae/ultrastructure , Saccharomyces cerevisiae Proteins/ultrastructureABSTRACT
The structures of over 30 complexes of Ras superfamily small GTP-binding proteins bound to diverse protein partners have been reported. Comparison of these complexes using the sequences of the small GTP-binding proteins to align the contact sites shows that virtually all surface positions make contacts with at least one partner protein. Rather than highlighting a single consensus binding site, these comparisons illustrate the remarkable diversity of contacts of Ras superfamily members. Here, a new analysis technique, the interface array, is introduced to quantify patterns of surface contacts. The interface array shows that small GTP-binding proteins are recognized in at least nine distinct ways. Remarkably, binding partners with similar functions, including those with distinct folds, recognize small GTP-binding proteins in similar ways. These classes of shared surface contacts support the occurrence of both divergent and convergent evolutionary processes and suggest that specific effector functions require particular protein-protein contacts.
