HEAT repeats associated with condensins, cohesins, and other complexes involved in chromosome-related functions

Abstract

HEAT repeats correspond to tandemly arranged curlicue-like structures that appear to serve as flexible scaffolding on which other components can assemble. Using sensitive sequence analysis techniques we detected HEAT repeats in various chromosome-associated proteins, including four families of proteins associated with condensins and cohesins, which are nuclear complexes that contain structural maintenance of chromosome (SMC) proteins. Among the proteins detected were the XCAP-D2 and XCAP-G subunits of the Xenopus laevis 13S condensin complex, the Aspergillus BimD and Sordaria macrospora Spo76p proteins, the budding yeast Scc2p protein, and the related Drosophila transcriptional activator Nipped-B. Clathrin adaptor and COP-I coatomer subunits, which function in vesicle coat assembly and were previously noted to share weak sequence similarity to condensin subunits, also contain HEAT repeats. HEAT repeats were also found in the TBP-associated TIP120 protein, a global enhancer of transcription, and in the budding yeast Mot1p protein, which is a member of the SWI2/SNF2 family. SWI2/SNF2 proteins, some of which are helicases, perform diverse roles in transcription control, DNA repair, and chromosome segregation and form chromatin-remodeling complexes. HEAT repeats also were found in dis1-TOG family and cofactor D family microtubule-associated proteins, which, owing to their roles in microtubule dynamics, perform functions related to mitotic progression and chromosome segregation. Hence, our analysis predicts structural features of these proteins and suggests that HEAT repeats may play important roles in chromosome dynamics.

Figure 1

Features of HEAT-repeat proteins. (a) Typical structure of a repeat. Sidechain atoms for more highly conserved positions are shown. The structure and sequence corresponds to repeat-10 of importin-β (1QGKA). (b) Schematic representation of domain architectures. HEAT repeats are colored red in proportion to their profile scores, using lighter shades for less conserved repeats. Protein names are colored by families. “Explosions” indicate compositionally biased regions and are shaded red for acidic, blue for basic, and green for uncharged polar biases. Other domains are as indicated.

Figure 2

Multiple alignment of HEAT repeats discussed in the text. For comparison, we also include the 16 HEAT repeats that were detected (and correctly aligned) by our procedures for human importin-β, whose structure is known (Cingolani et al. 1999; pdb code 1QGKA). For each aligned column, conserved residues—elevated with binomial tail probabilities (Neuwald and Green 1994) of p ≤ .0001—and less conserved, related residues—with tail probabilities of p ≤ .0005—are indicated using an automated hierarchical scheme (Neuwald et al. 1999) as follows: ≥1.25 bits of information, red highlight; 1.25–0.75 bits of information, magenta; ≥70% conserved and hydrophobic, yellow; >66% conserved, black; 50%–66% conserved, dark gray; 33%–50% conserved, black; <33% conserved, dark gray; unconserved, light gray.

Figure 2

Multiple alignment of HEAT repeats discussed in the text. For comparison, we also include the 16 HEAT repeats that were detected (and correctly aligned) by our procedures for human importin-β, whose structure is known (Cingolani et al. 1999; pdb code 1QGKA). For each aligned column, conserved residues—elevated with binomial tail probabilities (Neuwald and Green 1994) of p ≤ .0001—and less conserved, related residues—with tail probabilities of p ≤ .0005—are indicated using an automated hierarchical scheme (Neuwald et al. 1999) as follows: ≥1.25 bits of information, red highlight; 1.25–0.75 bits of information, magenta; ≥70% conserved and hydrophobic, yellow; >66% conserved, black; 50%–66% conserved, dark gray; 33%–50% conserved, black; <33% conserved, dark gray; unconserved, light gray.