The kinetochore is essential for the accurate segregation of sister chromosome in the eukaryote cell. Among the kinetochore subunits, five proteins CENP-O/P/U/Q/R form a stable complex, referred to as CENP-O class, and are required for proper kinetochore function. Although the function and structure of yeast COMA complex
In mitosis, the accurate segregation of sister chromosomes relies on kinetochore, a multiple subunits complex assembled on centromere of each sister chromosome. As a core component of inner kinetochore, CENP-I plays important functions to mediate kinetochore assembly and supports the faithful chromosome segregation. The structures of the N-terminus and C-terminus of CENP-I homologs in complex with CENP-H/K have been reported, respectively. Unfortunately, the intramolecular interactions of CENP-I are poorly understood, and how CENP-I interacts with CENP-M remains unknown. Here, we verified a unique helix α11, which forms the intramolecular interactions with N-terminal HEAT repeats in fungal CENP-I. Deletion of the helix α11 exposed the hydrophobic surface and resulted in the in vitro protein aggregation of N-terminal HEAT repeats of fungal CENP-I. The corresponding helix and its intramolecular interaction are highly conserved in human CENP-I. Deletion of the corresponding helix in human CENP-I dramatically reduced the functional activity to interact with CENP-H and CENP-M. Mutations of the conserved residues on the helix in human CENP-I significantly weakened the binding to CENP-M, but not CENP-H, in HeLa cells. Therefore, our findings for the first time unveiled a conserved helix of CENP-I, which is important for the intramolecular interaction and function, and would be helpful for understanding the structure basis of how CENP-I mediates the kinetochore assembly during cell cycle and mitosis. K E Y W O R D S centromere, computational protein structure, crystal structure, intramolecular interaction, kinetochore, protein-protein interaction
With the increase of short circuit current, measures should be taken to reduce the impact. Among various measures, a new technique to interrupt or limit current is proposed and applied to power grid based on high coupled split reactor (HCSR). As the key equipment in new technique, the insulation design of HCSR is a priority. Previous works mainly involve voltage across HCSR in different working states, and take the whole voltages as design requirements. It is rough and takes no account of voltage distribution inside HCSR, thus not suitable for insulation design of HCSR. In order to analyze the overvoltage problems and determine insulation demands for HCSR, this paper establishes the equivalent circuit model in turn unit to calculate the voltage distribution inside HCSR, which is simplified and accurate enough for HCSR. A 500 kV AC fault current limiter is briefly introduced, and voltages between turns or arms in HCSR are obtained. The voltage between turns are evenly distributed and voltage between arms are very low under switching impulse. As for lightning impulse, maximum turn-to-turn voltages mainly appear in the end of encapsulations, and the voltage between arms in current sharing state is considerable. This paper gives the calculation method and general rules of voltage distribution inside HCSR, and it has great significance for the insulation design of HCSR.
The enrichment of histone H3 variant CENP-A is the epigenetic mark of centromere and initiates the assembly of the kinetochore at centromere. The kinetochore is a multi-subunit complex that ensures accurate attachment of microtubule centromere and faithful segregation of sister chromatids during mitosis. As a subunit of kinetochore, CENP-I localization at centromere also depends on CENP-A. However, whether and how CENP-I regulates CENP-A deposition and centromere identity remains unclear. Here, we identified that CENP-I directly interacts with the centromeric DNA and preferentially recognizes AT-rich elements of DNA via a consecutive DNA-binding surface formed by conserved charged residues at the end of N-terminal HEAT repeats. The DNA binding–deficient mutants of CENP-I retained the interaction with CENP-H/K and CENP-M, but significantly diminished the centromeric localization of CENP-I and chromosome alignment in mitosis. Moreover, the DNA binding of CENP-I is required for the centromeric loading of newly synthesized CENP-A. CENP-I stabilizes CENP-A nucleosomes upon binding to nucleosomal DNA instead of histones. These findings unveiled the molecular mechanism of how CENP-I promotes and stabilizes CENP-A deposition and would be insightful for understanding the dynamic interplay of centromere and kinetochore during cell cycle.
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