Biological unit
From PDBWiki
In structural biology, the biological unit describes the functional form of a protein. This 'functional unit' could be a monomer, an oligomer or a complex, and is dependent on the definition of the natively active form of the protein. The necessity of this term stems from the difficulty of ascertaining the correct oligomeric state of a protein from its crystal structure.
Some synonyms are defined here for reference throughout the text;
- Biological unit
- biounit, functional unit, biological molecule, biological assembly, protein quaternary structure, oligomer, multisubunit protein, complex.
- Unit cell
- asymmetric unit, ASU.
- Crystal lattice
- lattice
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[edit] Protein structure determination
The majority of all protein structures are determined by x-ray crystallography. Although NMR continues to be an important method of structure determination, most protein structures are derived from experiments based on protein crystals. The majority of protein structures are, therefore, structures of the protein in the crystalline form. The form of a protein in the crystal may not be fully representative of the 'real' protein structure, depending on how we wish to define that.
A protein crystal is an orderly three-dimensional array of protein molecules, held together by noncovalent interactions. The crystal, by definition, can be divided into identical unit cells, and the array of unit cells is called the lattice. The unit cell is the simplest element that is completely representative of the whole crystal. The crystal can be described as an efficiently packed array of many unit cells stacked beside and on top of each other, more or less like identical boxes in a warehouse.
- Paragraph adapted From Crystallography made crystal clear. G Rhodes.
In other words, the unit cell is the smallest non-symmetrical part of the crystal that is repeated regularly in all directions.
Because of the inherent asymmetry of the unit cell (by definition) it is often referred to as the 'asymmetric unit' (often abbreviated to just 'ASU'). By convention, when a crystal structure is deposited in the PDB, only the asymmetric unit (ASU) is deposited. In addition, the crystallographic symmetry operations that relate the ASU to the crystal are included. This overcomes the technical issue of depositing data based on the theoretically infinite crystal structure using finite disk space.
[edit] Analysis of the ASU
The ASU is used for purely technical reasons and may not represent what we commonly think of as 'a functional protein'. For example, if a protein is known to function in-vivo as a homo-dimer (formed by two copies of the same polypeptide chain), it may be (and often is) the case that in the crystal structure the dimer interface is symmetrical. In 2D that would look something like "dp", where "d" is one copy of the polypeptide chain, and "p" is an identical copy, rotated by 180 degrees and translated a bit.
In this case the 'biological unit' is given by two copies of the ASU related by a given symmetry operation (in this case, rotate by 180 degrees and shift over by 1 unit). Now lets assume that this dimer is crystallized in the presence of a substrate analogue, giving "d¬p". Note that the substrate is bound asymmetrically by the symmetrical interface! In this case the ASU would be a full biological unit!
This concept is described in more detail here; http://pqs.ebi.ac.uk/pqs-doc/pqs-doc.shtml
[edit] When is an oligomer not an oligomer?
It has long been known that some proteins exist as complex assemblies of polypeptide subunits (Svedberg 1929, Kendrew 1960, Perutz 1960). These multisubunit protein oligomers are formed by stable and specific non-covalent subunit-subunit associations that often form symmetrical assemblies (Crick 1956, Monod 1965). Similar non-covalent associations often form in protein signaling pathways, and such interactions are essential to almost every conceivable biological process.
As described above, most proteins in the PDB have three or more crystal contacts that sum to approximately 30\% of the proteins solvent assessable surface area (ASA), probably as a requirement for the stability of the crystal (Carugo 1997). For this reason, the correct, 'biologically significant' oligomeric state is often uncertain from the structure of the crystal.
Several groups have tackled the problem of discriminating biologically significant protein assemblies in the PDB from crystal contacts (Janin 1995, Carugo 1997, Dasgupta 1997, Henrick 1998, Ponstingl 2000, Valdar 2001, Mintseris 2003, Bahadur 2004, Rodier 2005, Krissinel 2005).
Many properties have been used to discriminate between crystal packing and biologically significant interafaces, including hydrophobicity, shape analysis, amino acid pair preferences, and number of hydrogen bonds. The problem of determining the biologically significant assemblies is exacerbated by the fact that entries in the PDB often have an uncertain or unknown oligomeric state (henrick 1998).
[edit] References
[edit] External Links
- The wp:Biological unit article on Wikipedia.
- The wp:Quaternary structure article on Wikipedia.
- A description of of the relationship between the BioUnit and the ASU [1].
- The Biological Unit article on proeteopedia.
[edit] Databases of predicted protein quaternary structures
In no particular order:
- The Protein Quaternary Structure Server (PQS) [2] or [3]
- The Macro-Molecular Structure Database (MSD) [4] or [5]
- The Protein Interfaces, Surfaces and Assemblies server (Pisa) [6]
- Protein quaternary structure investigation (PiQSi) [7]
