Crystal structure of the LUFS domain of human single-stranded DNA binding Protein 2 (SSBP2)

Hongyang Wang1,2,3, Zhizhi Wang3, Qun Tang1

  • 1National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.

Insights

The study reveals the 3D structure of the human SSBP2 LUFS domain, showing it forms a homo-tetramer. This finding explains how the protein tetramerizes, a mechanism potentially shared by other LUFS domains.

Area of Science:

  • Structural Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Human single-stranded DNA binding Protein 2 (SSBP2) acts as a tumor suppressor.
  • SSBP2 and related proteins contain a conserved N-terminal LUFS domain, crucial for function but lacking structural data.
  • LUFS domains, featuring a LisH motif, are present in transcriptional co-repressors.

Purpose of the Study:

  • To determine the 3D structure of the human SSBP2 LUFS domain.
  • To elucidate the oligomerization state and mechanism of the SSBP2 LUFS domain.
  • To investigate the structural basis for LUFS domain interactions.

Main Methods:

  • X-ray crystallography was employed to obtain the crystal structure.
  • High-resolution (1.52 Å) structural analysis was performed.
  • Bioinformatic analysis of conserved interfaces was conducted.

Main Results:

  • The crystal structure of the human SSBP2 LUFS domain was determined.
  • The SSBP2 LUFS domain was shown to form a homo-tetramer.
  • An alpha-helix C-terminal to the LisH motif was identified as mediating tetramerization.

Conclusions:

  • The SSBP2 LUFS domain forms a stable homo-tetramer through a novel mechanism involving a C-terminal alpha-helix.
  • This tetramerization interface is conserved among LUFS domains, suggesting a common oligomerization strategy.
  • The structural insights provide a foundation for understanding SSBP2 function in cancer and other cellular processes.

Related Concept Videos

Single-Strand DNA Binding Proteins01:03

Single-Strand DNA Binding Proteins

For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
16.7K
Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
14.4K
Ionic Crystal Structures02:42

Ionic Crystal Structures

Ionic crystals consist of two or more different kinds of ions that usually have different sizes. The packing of these ions into a crystal structure is more complex than the packing of metal atoms that are the same size.
Most monatomic ions behave as charged spheres, and their attraction for ions of opposite charge is the same in every direction. Consequently, stable structures for ionic compounds result (1) when ions of one charge are surrounded by as many ions as possible of the opposite...
17.0K
From DNA to Protein03:06

From DNA to Protein

The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...
22.3K
Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
14.6K
DNA Helicases00:55

DNA Helicases

DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
24.1K