17-May-2022 - Max-Planck-Institut für molekulare Physiologie

Structure of key protein for cell division puzzles researchers

Researchers provide a first 3D snapshot of the CCAN protein complex and raise fundamental questions towards the creation of artificial chromosomes

Human cell division involves hundreds of proteins at its core. Knowing the 3D structure of these proteins is pivotal to understand how our genetic material is duplicated and passed through generations. The groups of Andrea Musacchio and Stefan Raunser at the Max Planck Institute of Molecular Physiology in Dortmund are now able to reveal the first detailed structure of a key protein complex for human cell division known as CCAN. By using cryo-electron microscopy, the researchers show important features of the complex’s 16 components and challenge previous assumptions about how the complex is able to recognize the centromere, a crucial region of chromosomes in cell division.

At the centre of cell division

The centromere is a constriction in the chromosome, made of DNA and proteins. Most importantly, the centromere is the dock for the kinetochore, a machinery of about 100 proteins that drives the separation of two identical chromosomes during cell division and their delivery to the daughter cells. Previous research has shown that the kinetochore docks onto the centromere through the CCAN complex: The CCAN interacts with the centromere protein A, the landmark protein of the centromere. CCAN is also responsible for replenishing the centromere protein A once the cell division has taken place. Yet, the details of the interaction between CCAN and the centromere protein A remain elusive. “Understanding how CCAN recognises and binds to the centromere could potentially lead us to build a centromere from scratch”, says Musacchio. The centromere is a major hurdle for synthetic biologists who aim to engineer artificial chromosomes to restore missing functions or introduce new ones in cells.

Unresolved questions at the core

Scientists identified the CCAN complex over 15 years ago. “Yet, building up a pipeline to synthesize all proteins in vitro has been a major obstacle”, says Musacchio. After obtaining a first reconstitution of the human CCAN complex in vitro, Musacchio joined forces with Stefan Raunser, also at MPI Dortmund, who applied cryo-electron microscopy on the whole CCAN protein complex.

In the new publication, the MPI groups have been able to determine the 3D structural details of the human CCAN complex, highlighting its unique features and the implications for an interaction with the centromere protein A. “Contrary to what was expected, this structure does not directly recognise the centromere protein A in the standard configuration”, says Musacchio. The centromere protein A is most commonly packed with DNA and other proteins as a nucleosome, the standard unit of the genetic material. The authors are now suggesting that the centromere protein A may be embedded in the centromere with a different configuration that may facilitate the crucial interaction with CCAN. They plan to identify conditions that could lead to this new configuration and prove their hypothesis.

Facts, background information, dossiers

  • cell division
  • proteins
  • protein complexes
  • cryo-electron microscopy
  • protein synthesis

More about MPI für molekulare Physiologie

  • News

    A new dimension in Stem Cell Signaling

    Divide, differentiate or die? Making decisions at the right time and place is what defines a cell’s behavior and is particularly critical for stem cells of an developing organisms. Decision making relies on how information is processed by networks of signaling proteins. The teams around Chr ... more

    Cool Microscopy: Making the invisible visible

    Fluorescence light microscopy has the unique ability to observe cellular processes over a scale that bridges four orders of magnitude. Yet, its application to living cells is fundamentally limited by the very rapid and unceasing movement of molecules and the light-induced destruction of flu ... more

    Stem cells do not (only) play dice

    In just a few weeks a completely new organism develops from a fertilized egg cell. The real miracle is that a bunch of identical stem cells turns into completely different, specialized cell types. A team led by Christian Schröter, group leader at the Max Planck Institute of Molecular Physio ... more

More about Max-Planck-Gesellschaft

  • News

    Pumping up the music of molecules

    Sensitive animal noses can sniff out trace particles, such as volatile organic compounds, in the ambient air. Humans, on the other hand, are developing innovative technologies for this purpose, such as optical spectroscopy. This uses laser light to detect the molecular composition of gases. ... more

    How to find marker genes in cell clusters

    The thousands of cells in a biological sample are all different and can be analyzed individually, cell by cell. Based on their gene activity, they can be sorted into clusters. But which genes are particularly characteristic of a given cluster, i.e. what are its “marker genes”? A new statist ... more

    Cell-culture breakthrough: Advanced “mini brains” in the dish

    “Outer Radial Glia” (oRG) cells are nervous system stem cells that are instrumental for the development of the human cortex and have been challenging to produce in the lab. Now, a team of Max Planck researchers from Berlin succeeded in generating brain organoids that are enriched with these ... more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by: