Figure 1.
Overall organization of the S. cerevisiae KMN junction complex.(A) Subcomplex and subunit composition of the S. cerevisiae KMN complex. (B) Composite cryo-EM density map of the S. cerevisiae KMN junction complex derived from docking the apex and base bodies (Fig. S2 Diii) into the consensus density map. (C) Model of the KMN junction complex, highlighting the motifs that mediate the interactions between Mis12cMtw1c and Knl1c or Ndc80c. (D and E) Comparison of cryo-EM structures of the inactive S. cerevisiae KMN junction complex with head 2 and Dsn1AI defined (this study) (D) with the inactive human KMN junction complex (PDB: 8PPR) from Yatskevich et al. (2024) (E). Structures shown in D and E were superimposed on the stalk segment (CC2, CC3) of the Mis12/Mis12Mtw1 chain. (F) Cartoon schematic of the S. cerevisiae KMN junction complex, based on the structures determined in this study. The interactions between Mis12Mtw1_Cterm-helix and Knl1Spc105_RWD-N; Nnf1Cterm-helix and Knl1Spc105_RWD-C; and Dsn1Cterm-helix and Mtw1Spc24-helix and the Spc24 and 25 RWD domains, and Mis12cMtw1c and the two auto-inhibitory α-helices in DsnAI, and CENP-CMif2 and CENP-QAme1–binding sites are highlighted. The four interfaces discussed in the text are numbered in parenthesis. (G) Cartoon schematic of the human KMN junction complex, based on the structures determined in Yatskevich et al. (2024) (PDB: 8PPR). Interactions between Nsl1Cterm and Knl1c; Mis12c stalk CC3 region and Knl1RWD-C; and Dsn1Cterm-helix and Nsl1Spc24-helix and the Spc24 and 25 RWD domains, and Mis12c head 1 and Dsn1AI, and CENP-C–binding site are highlighted. Refer to the image caption for details. Panel A shows diagram of subcomplex and subunit composition including K n l 1 c, N d c 80 c, and M i s 12 c modules; Panel B shows composite cryo-E M density map of the yeast K M N junction complex; Panel C shows structural model highlighting interaction motifs between M i s 12 c M t w 1 c and K n l 1 c or N d c 80 c; Panel D shows cryo-E M structure of inactive yeast K M N junction with defined head 2 and D s n 1 auto-inhibitory region; Panel E shows cryo-E M structure of inactive human K M N junction aligned with yeast along the M i s 12 stalk (C C 2, C C 3); Panel F shows cartoon schematic of yeast K M N junction highlighting interaction interfaces and binding sites including C E N P-C (M i f 2) and C E N P-Q (A m e 1); Panel G shows cartoon schematic of human K M N junction illustrating conserved interactions among N s l 1, K n l 1, D s n 1 and C E N P-C.

Overall organization of the S. cerevisiae KMN junction complex. (A) Subcomplex and subunit composition of the S. cerevisiae KMN complex. (B) Composite cryo-EM density map of the S. cerevisiae KMN junction complex derived from docking the apex and base bodies (Fig. S2 Diii) into the consensus density map. (C) Model of the KMN junction complex, highlighting the motifs that mediate the interactions between Mis12cMtw1c and Knl1c or Ndc80c. (D and E) Comparison of cryo-EM structures of the inactive S. cerevisiae KMN junction complex with head 2 and Dsn1AI defined (this study) (D) with the inactive human KMN junction complex (PDB: 8PPR) from Yatskevich et al. (2024) (E). Structures shown in D and E were superimposed on the stalk segment (CC2, CC3) of the Mis12/Mis12Mtw1 chain. (F) Cartoon schematic of the S. cerevisiae KMN junction complex, based on the structures determined in this study. The interactions between Mis12Mtw1_Cterm-helix and Knl1Spc105_RWD-N; Nnf1Cterm-helix and Knl1Spc105_RWD-C; and Dsn1Cterm-helix and Mtw1Spc24-helix and the Spc24 and 25 RWD domains, and Mis12cMtw1c and the two auto-inhibitory α-helices in DsnAI, and CENP-CMif2 and CENP-QAme1–binding sites are highlighted. The four interfaces discussed in the text are numbered in parenthesis. (G) Cartoon schematic of the human KMN junction complex, based on the structures determined in Yatskevich et al. (2024) (PDB: 8PPR). Interactions between Nsl1Cterm and Knl1c; Mis12c stalk CC3 region and Knl1RWD-C; and Dsn1Cterm-helix and Nsl1Spc24-helix and the Spc24 and 25 RWD domains, and Mis12c head 1 and Dsn1AI, and CENP-C–binding site are highlighted.

This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal