The
dynein-driven beating of cilia is required to move individual cells and to generate fluid flow across surfaces and within cavities. These motor
enzymes are highly complex and can contain upwards of 20 different
protein components with a total mass approaching 2 MDa. The
dynein heavy chains are enormous
proteins consisting of ~4500 residues and ribosomes take approximately 15 min to synthesize one. Studies in a broad array of organisms ranging from the green alga Chlamydomonas to humans has identified 19 cytosolic factors (DNAAFs) that are needed to specifically build
axonemal dyneins; defects in many of these
proteins lead to
primary ciliary dyskinesia in mammals which can result in
infertility, severe bronchial problems, and
situs inversus. How all these factors cooperate in a spatially and temporally regulated manner to promote
dynein assembly in cytoplasm remains very uncertain. These DNAAFs contain a variety of well-folded domains many of which provide
protein interaction surfaces. However, many also exhibit large regions that are predicted to be inherently disordered. Here I discuss the nature of these unstructured segments, their predicted propensity for driving
protein phase separation, and their potential for adopting more defined conformations during the
dynein assembly process.