Surreal illustration of chromosome organization with condensin protein structures.

Unlocking Life's Code: New 3D Model Illuminates How Chromosomes Organize

Nico Varela in Science & Nature December 2025 • 5 min read.

"Scientists create the first complete atomic-level structure of the bacterial condensin complex, revealing the secrets of chromosome segregation and potential for future biotech innovations."

Imagine the nucleus of a cell as a meticulously organized library, where each chromosome is a carefully arranged collection of genetic information. The structural integrity of these chromosomes is paramount for accurate cell division and overall health. Enter condensin, a protein complex crucial for compacting and segregating chromosomes in all living organisms.

For years, scientists have been piecing together the puzzle of how condensin works. This complex, composed of SMC (structural maintenance of chromosomes) and kleisin subunits, ensures that chromosomes are properly segregated during cell division. Errors in this process can lead to genetic disorders and diseases like cancer. However, until now, a complete picture of condensin's structure has remained elusive.

Now, a team of researchers has achieved a significant breakthrough by developing an atomic-scale structure of the entire condensin complex. By combining crystallographic data with coevolutionary information, they've created a 3D model that reveals the complex's architecture and sheds light on its functional mechanisms. This discovery paves the way for future investigations into the structure-function relationship of SMC-kleisin protein complexes and their role in maintaining genomic stability.

Deciphering the Condensin Complex: A Single Ring Structure

Surreal illustration of chromosome organization with condensin protein structures.

The research team's integrative approach combined existing crystallographic data of condensin subunits with coevolutionary information derived from bacterial SMC-ScpAB protein complexes. Coevolutionary analysis identifies correlated mutations in different protein subunits that are likely to interact physically and functionally. These correlations can provide valuable clues about the spatial arrangement of proteins within a complex.

Using direct coupling analysis (DCA), the researchers predicted residue contacts within the condensin complex. This method statistically models sequence data to disentangle complex cross-correlations between amino acids, revealing which pairs are most likely to be spatially proximate. The team then validated their approach by comparing the DCA-predicted contacts with known physical contacts from crystal structures of individual subunits, confirming the accuracy of their predictions.

Single Ring Confirmation: The study strongly supports a single-ring structure for the bacterial condensin complex, where a single ScpA subunit interacts with an ScpB dimer and two SMC head domains. This model aligns with structural and coevolutionary data.
Alternative Stoichiometries Debunked: The research challenges alternative models, such as the double-ring structure. Simulations showed that a double-ring configuration is inconsistent with coevolutionary constraints.
ScpAB Subcomplex Formation: The analysis suggests a specific order of events for the assembly of the ScpAB subcomplex, where ScpA first binds to one ScpB protein, followed by the second, highlighting the dynamics of complex formation.

Furthermore, the team identified several hinge configurations within the SMC domains, which are likely involved in the functional opening and closing of the condensin ring. These configurations, revealed through DCA, suggest potential mechanisms for DNA entry and exit. By analyzing the arrangement of charged amino acids in these configurations, the researchers proposed how condensin might interact with DNA's negatively charged phosphate groups.

Implications and Future Directions

This groundbreaking 3D model provides a crucial framework for understanding how condensin organizes and segregates chromosomes. By mapping the interaction surfaces between subunits and identifying key hinge configurations, the study offers insights into the dynamic mechanisms that drive chromosome maintenance.

The findings also have significant implications for biotechnology and medicine. A better understanding of condensin's structure-function relationship could lead to new strategies for manipulating chromosome structure in genetic engineering or for developing targeted therapies for diseases caused by chromosome instability, such as cancer.

Future research will focus on further elucidating the dynamics of the condensin complex and its interactions with DNA. By combining this structural information with functional assays and cellular imaging techniques, scientists can gain a more comprehensive understanding of how condensin orchestrates chromosome segregation and maintains genomic integrity.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1073/pnas.1812770115, Alternate LINK

Title: Deciphering The Structure Of The Condensin Protein Complex

Subject: Multidisciplinary

Journal: Proceedings of the National Academy of Sciences

Publisher: Proceedings of the National Academy of Sciences

Authors: Dana Krepel, Ryan R. Cheng, Michele Di Pierro, José N. Onuchic

Published: 2018-11-01

Everything You Need To Know

What is the bacterial condensin complex and what does it do?

The bacterial condensin complex is a protein complex comprised of SMC and kleisin subunits. Its primary function is to compact and segregate chromosomes during cell division. This process is essential for maintaining genomic stability and preventing genetic disorders and diseases like cancer. Errors in chromosome segregation, which condensin helps prevent, can have significant implications for cell health and overall organismal well-being.

What did the researchers achieve, and why is this important?

The research team's achievement is a complete atomic-scale 3D model of the bacterial condensin complex. This model was created by integrating crystallographic data of condensin subunits with coevolutionary information from bacterial SMC-ScpAB protein complexes. The 3D model offers a comprehensive view of the complex's architecture, providing unprecedented insights into its functional mechanisms. This is significant because it allows researchers to understand how the condensin works at the atomic level, which helps explain how chromosomes are organized and segregated, paving the way for future investigations into the structure-function relationship of SMC-kleisin protein complexes and their role in maintaining genomic stability.

What is the single-ring structure of the condensin complex, and why is it significant?

The single-ring structure for the bacterial condensin complex is supported by the research. In this model, a single ScpA subunit interacts with an ScpB dimer and two SMC head domains. The research team's model, however, has debunked alternative models such as the double-ring structure. Simulations showed that a double-ring configuration is inconsistent with coevolutionary constraints. Identifying the correct structure is crucial because it informs the understanding of how the condensin complex functions in chromosome organization and segregation. Accurate models lead to more effective research.

How is coevolutionary analysis used in the study of the condensin complex?

Coevolutionary analysis is used in this context to identify correlated mutations within the bacterial condensin complex. These correlations help researchers predict which protein subunits are likely to interact physically and functionally. This information provides clues about the spatial arrangement of proteins within the complex. Direct coupling analysis (DCA) statistically models sequence data to reveal which amino acid pairs are most likely to be spatially proximate, which is validated with known physical contacts from crystal structures, to determine the arrangement of the complex, and the formation of the ScpAB subcomplex.

What are hinge configurations in the SMC domains, and why are they significant?

Hinge configurations within the SMC domains are likely involved in the functional opening and closing of the condensin ring. These configurations, revealed through direct coupling analysis, suggest potential mechanisms for DNA entry and exit. The identification of these hinge configurations and the arrangement of charged amino acids offers insights into how condensin might interact with DNA's negatively charged phosphate groups. Understanding these dynamics helps in understanding how the condensin complex functions, which impacts chromosome maintenance.