3D structure of regulator protein revealed
Research team creates molecular basis for a better understanding of the regulation of cellular degradation processes

Date:
February 2, 2022
Source:
University of Mu"nster
Summary:
A team of researchers has revealed the structure of a protein
complex which is an important regulator of cellular degradation
processes.



FULL STORY ========================================================================== Proteins are indispensable components in living organisms. They are
not only "building material" for the body -- they also make molecular communication between cells possible, they are needed for nerve impulses
to occur, and they control chemical reactions. What is decisive for
proteins to function is their three-dimensional structure. If this is
known, conclusions can be drawn about how proteins function. A team of researchers led by Prof. Daniel Ku"mmel from the University of Mu"nster
and Prof. Stefan Raunser from the Max Planck Institute (MPI) of Molecular Physiology in Dortmund (Germany) has now clarified the structure of a
protein complex which is an important regulator of cellular degradation processes.


==========================================================================
The protein complex "Mon1/Ccz1" determines which intracellular vesicles
deliver their content to the cellular "recycling centre," the lysosome. To
this end, it docks onto the vesicle membrane, where it introduces a
label. Intracellular vesicles are membrane bubbles which transport
material through the cell. In the lysosome, the content is degraded
and re-used. By elucidating the structure in almost atomic resolution,
the researchers were now able to clarify, among other things, how the
protein complex recognises the appropriate vesicles. For example, they
showed that the complex has a positively charged and relatively flat area
which determines its orientation after docking onto the vesicle membrane.

"Mon1/Ccz1" belongs to a family of regulators for which no structural information exists. These complexes are involved in a range of
cellular processes and are sometimes associated with the occurrence
of developmental disorders such as albinism and blood clotting
disorders. "Our structure now provides a basis for a better understanding
of these connections," says Daniel Ku"mmel.

The protein complex examined comes from the filamentous fungus
Chaetomium thermophilum and is particularly stable and easy to
handle under laboratory conditions. It can serve as a model for human
proteins. In order to determine the protein's structure, the researchers
used high-resolution cryogenic electron microscopy. "With this method,
we can study the structure of proteins at temperatures around minus 150
degrees Celsius in an almost natural state," says Stefan Raunser.

The researchers checked their results by means of biochemical studies,
for example sedimentation assays. In this case, the protein-membrane interaction is demonstrated with artificial vesicles and purified protein
in vitro, i.e.

outside the organism. "The structure of Mon1/Ccz1 has a unique
architecture that, to our knowledge, has not been demonstrated in any
other protein complex.

It could serve as a blueprint for a better understanding of other related regulatory proteins. We want to continue our successful collaboration,"
Daniel Ku"mmel and Stefan Raunser agree.

The study was published in the interdisciplinary journalProceedings of
the National Academy of Sciences. In addition to scientists from WWU
Mu"nster and MPI Dortmund, researchers from the University of Osnabru"ck
were also involved.

========================================================================== Story Source: Materials provided by University_of_Mu"nster. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Bjo"rn U. Klink, Eric Herrmann, Claudia Antoni, Lars Langemeyer,
Stephan
Kiontke, Christos Gatsogiannis, Christian Ungermann, Stefan Raunser,
Daniel Ku"mmel. Structure of the Mon1-Ccz1 complex reveals molecular
basis of membrane binding for Rab7 activation. Proceedings of
the National Academy of Sciences, 2022; 119 (6): e2121494119 DOI:
10.1073/ pnas.2121494119 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220202091933.htm

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