Lecture 6 Flashcards
Protein Assemblies
Big Picture Items
- Many proteins contain multiple chains, called subunits
- Subunits can contain one or more domains
- Multi-subunit proteins are often symmetric
- Multi-subunit proteins can also be non-symmetric
- Chaperones can assist the protein folding process
- Some chaperones are complex molecular machines
- Protein misfolding can lead to major diseases
Quaternary Structure
- The arrangement of multiple protein chains into a multi-protein assembly is called the quaternary structure of that assembly.
- The protein chains of an assembly are called subunits
• In living cells, many multi-protein assemblies occur.
The advantages of bringing multiple proteins together include:
• multiple functions can be brought in close proximity
(e.g., multi-enzyme complexes and bacterial toxins)
• cages of sufficient size can be created
(e.g. chaperones and viral capsids)
• long fibers can be obtained
(e.g. microfilaments)
- Multi-protein and protein-nucleic acid assemblies can:
- have symmetry, or partial symmetry, or no symmetry
- consist of multiple copies of a single, or of a few, or of numerous different proteins.
- contain a combination of protein and nucleic acid chains
Helical symmetry
rotation about an axis and a translation along that axis
biomacromolecules no mirror symmetry occurs
(due to chirality of biomolecules!)
In point group symmetry, all symmetry axes
intersect in one point, the center of the particle
A Trimer with cyclic C3 Point Group Symmetry
Haemagglutinin
From the surface of the influenza virus
A Heptamer with cyclic C7 Point Group Symmetry
GroES
The “cap” of a protein folding machine
A single seven-fold axis relates the seven subunits in this heptamer.
Dihedral Point Group Symmetry
Dihedral symmetry:
- Start with an object with cyclic symmetry.
- Add a twofold axis perpendicular to the axis in the starting object.
- Additional 2-fold axes perpendicular to the initial symmetry axis (i.e. the vertical axis above) are generated.
GroEL: The “body” of a protein folding machine, a 14-mer
Polyhedral Symmetry: Tetrahedral symmetry
- Symmetry group based on a tetrahedron
- 3-fold at each vertex
- 3-fold at each face
- 2-fold at each edge
• If there is one subunit type, then a complex
contains 12 subunits
2-fold and 3-fold rotation axes
Polyhedral Symmetry: Octahedral symmetry
• Symmetry group based on a octahedron (alternate description using a cube) • 4-fold at each vertex • 3-fold at each face • 2-fold at each edge
• If there is one subunit type, then a complex contains 24 subunits
2-fold, 3-fold and 4-fold rotation axes
Polyhedral Symmetry: Icosahedral symmetry
• Symmetry group based on an icosahedron (alternate description using a dodecahedron) • 5-fold at each vertex • 3-fold at each face • 2-fold at each edge
• If there is one subunit type, then a complex
contains 60 subunits
2-folds, 3-fold and 5-fold rotation axes
An enzyme with octahedral symmetry
- The core of the pyruvate dehydrogenase complex
* Forms a “hollow cube”
Some viruses have icosahedral symmetry
Icosahedral symmetry generates 60 equivalent objects out of ONE object.
There are 20 triangles per icosahedron, so from the figure above it is quite easy to calculate that there are 60 golden objects with the shape of a “1” per icosahedron
Spherical viruses with icosahedral symmetry have often Nx60 equivalent protein subunits in the capsid surrounding the RNA or DNA in a virus particle (where N is an integer).
The virus above has
3x60=180 proteins in its “capsid”.
Inside the capsid above is the viral RNA.
Poliovirus looks like the virus above (ball like)
Helical Symmetry Yields Fibers
Fibrous Proteins are Crucially Important for Cell Integrity and Rigidity, as well as for Adhesion and Mobility.
Examples:
- actin in microfilaments and muscle
- pilins in pili (also called fimbriae) on the surface of bacteria
Fiber formation is exquisitely well controlled in living cells,
since otherwise the framework of the entire cell is in deep trouble!
(We will see later the devastating consequences from lack of control with Sickle Cell Hemoglobin)
Microfilaments are made of “Actin polymers”
Scanning electron micrograph of a crawling macrophage in the course of engulfing Staphylococcus bacteria (orange). The cell’s leading edge is at the top.
Rate of actin polymerization is greatest at the leading edge.
A macrophage is a white blood cell, crucial for the defense against pathogenic bacteria.
fibroblast
colored by fluorescent labeled anti-actin antibodies then viewed by fluorescent microscopy
A fibroblast is a cell that synthesizes the extracellular matrix and collagen.
Actin is the most abundant cytosolic protein in eukaryotic cells.
Three-dimensional structure of an actin subunit
Globular Actin (G-Actin) is a four-domain protein of ~ 375 amino acid residues. It binds ATP which it can hydrolyze. It also binds calcium.
Its most important property is to be able to assemble, and disassemble, into fibers, called microfilaments in non-muscle cells.
Right-hand figure: Ea
ch golden cube-like object represents a domain.
The large sphere in the center represents bound ATP; the small sphere the Mg2+ or Ca2 + ion
Three-dimensional structure of an actin subunit
