Crystal structure of transforming growth factor-beta 2: an unusual fold for the superfamily

S Daopin1, K A Piez, Y Ogawa

  • 1Laboratory of Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.

Science (New York, N.Y.)
|July 17, 1992
PubMed

Insights

The crystal structure of transforming growth factor-beta 2 (TGF-beta 2) reveals an elongated fold stabilized by disulfide bonds and hydrophobic interactions. This structure suggests other TGF-beta superfamily members share a similar fold, crucial for cell regulation.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Molecular Biology

Background:

  • Transforming growth factors-beta (TGF-beta) are critical cytokines regulating cell proliferation and function.
  • Members of the TGF-beta family exhibit high sequence identity and conserved cysteines, suggesting conserved structural features.

Purpose of the Study:

  • To determine the three-dimensional crystal structure of TGF-beta 2.
  • To elucidate the structural basis for TGF-beta 2 dimerization and stability.
  • To infer the conserved structural fold within the TGF-beta superfamily.

Main Methods:

  • X-ray crystallography at 2.1 angstrom resolution.
  • Refinement of the crystal structure.
  • Sequence profile analysis of TGF-beta superfamily members.

Main Results:

  • The TGF-beta 2 monomer exhibits an elongated, nonglobular fold (approx. 60x20x15 A) lacking a defined hydrophobic core.
  • Eight cysteines form four intrachain disulfide bonds clustered in a core region.
  • The dimer is stabilized by a ninth interchain disulfide bond and two hydrophobic interfaces.

Conclusions:

  • The determined TGF-beta 2 structure provides insights into the molecular mechanisms of cytokine regulation.
  • The unusual fold and stabilization by disulfide bonds are key features of TGF-beta 2.
  • Sequence analysis implies that other TGF-beta superfamily members likely adopt a similar conserved fold.

Related Concept Videos

Protein Folding01:22

Protein Folding

Overview
Structures of Solids02:22

Structures of Solids

Solids in which the atoms, ions, or molecules are arranged in a definite repeating pattern are known as crystalline solids. Metals and ionic compounds typically form ordered, crystalline solids. A crystalline solid has a precise melting temperature because each atom or molecule of the same type is held in place with the same forces or energy. Amorphous solids or non-crystalline solids (or, sometimes, glasses) which lack an ordered internal structure and are randomly arranged. Substances that...
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...
Crystal Field Theory - Tetrahedral and Square Planar Complexes02:46

Crystal Field Theory - Tetrahedral and Square Planar Complexes

Tetrahedral Complexes
Crystal field theory (CFT) is applicable to molecules in geometries other than octahedral. In octahedral complexes, the lobes of the dx2−y2 and dz2 orbitals point directly at the ligands. For tetrahedral complexes, the d orbitals remain in place, but with only four ligands located between the axes. None of the orbitals points directly at the tetrahedral ligands. However, the dx2−y2 and dz2 orbitals (along the Cartesian axes) overlap with the ligands less than the dxy,...
Protein and Protein Structure02:15

Protein and Protein Structure

Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme can...
Unit Cells01:18

Unit Cells

A crystal's internal structure is an orderly array of atoms, ions, or molecules, and the details of this array significantly influence the solid's properties. In a crystal, periodically repeating 'structural motifs' - which could be atoms, molecules, or groups thereof - create a 'space lattice.' This is essentially a three-dimensional, infinite array of points, each surrounded by its neighbors in an identical way, forming the basic structure of the crystal.A 'unit cell' is a theoretical...