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Protein structure is the biomolecular structure of a protein molecule. Each protein is a polymer – specifically a polypeptide – that is a sequence formed from various L-α-amino acids (also referred to as residues). By convention, a chain under 40 residues is often identified as a peptide, rather than a protein. To be able to perform their biological function, proteins fold into one or more specific spatial conformations, driven by a number of non-covalent interactions such as hydrogen bonding, ionic interactions, Van der Waals forces, and hydrophobic packing. To understand the functions of proteins at a molecular level, it is often necessary to determine their three-dimensional structure. This is the topic of the scientific field of structural biology, which employs techniques such as X-ray crystallography, NMR spectroscopy, and dual polarisation interferometry to determine the structure of proteins.
Protein structures range in size from tens to several thousand residues  Proteins are classified by their physical size as nanoparticles (definition: 1–100 nm). Very large aggregates can be formed from protein subunits: for example, many thousand actin molecules assemble into a microfilament.
A protein may undergo reversible structural changes in performing its biological function. The alternative structures of the same protein are referred to as different conformations, and transitions between them are called conformational changes.
Levels of protein structure 
There are four distinct levels of protein structure.
Primary structure 
The primary structure refers to amino acid linear sequence of the polypeptide chain. The primary structure is held together by covalent bonds such as peptide bonds, which are made during the process of protein biosynthesis or translation. The two ends of the polypeptide chain are referred to as the carboxyl terminus (C-terminus) and the amino terminus (N-terminus) based on the nature of the free group on each extremity. Counting of residues always starts at the N-terminal end (NH2-group), which is the end where the amino group is not involved in a peptide bond. The primary structure of a protein is determined by the gene corresponding to the protein. A specific sequence of nucleotides in DNA is transcribed into mRNA, which is read by the ribosome in a process called translation. .The sequence of amino acids was discovered by F.SANGER.The sequence of a protein is unique to that protein, and defines the structure and function of the protein. The sequence of a protein can be determined by methods such as Edman degradation or tandem mass spectrometry. Often however, it is read directly from the sequence of the gene using the genetic code. We know that there are over 10,000 proteins in our body which are composed of different arrangements of 20 types of amino acid residues (it is strictly recommended to use the word "amino acid residues" as when peptide bond is formed a water molecule is lost so, protein is made up of amino acid residues). Post-translational modifications such as disulfide formation, phosphorylations and glycosylations are usually also considered a part of the primary structure, and cannot be read from the gene. Example: Insulin is composed of 51 amino acids in 2 chains.One chain has 31 amino acids and the other has 20 amino acids.
Amino acid residues 
Each α-amino acid consists of a backbone part that is present in all the amino acid types, and a side chain that is unique to each type of residue. An exception from this rule is proline. Because the carbon atom is bound to four different groups it is chiral, however only one of the isomers occur in biological proteins. Glycine however, is not chiral since its side chain is a hydrogen atom. A simple mnemonic for correct L-form is "CORN": when the Cα atom is viewed with the H in front, the residues read "CO-R-N" in a clockwise direction.
Secondary structure 
Secondary structure refers to highly regular local sub-structures. Two main types of secondary structure, the alpha helix and the beta strand or beta sheets, were suggested in 1951 by Linus Pauling and coworkers. These secondary structures are defined by patterns of hydrogen bonds between the main-chain peptide groups. They have a regular geometry, being constrained to specific values of the dihedral angles ψ and φ on the Ramachandran plot. Both the alpha helix and the beta-sheet represent a way of saturating all the hydrogen bond donors and acceptors in the peptide backbone. Some parts of the protein are ordered but do not form any regular structures. They should not be confused with random coil, an unfolded polypeptide chain lacking any fixed three-dimensional structure. Several sequential secondary structures may form a "supersecondary unit".
Tertiary structure 
Tertiary structure refers to three-dimensional structure of a single protein molecule. The alpha-helices and beta-sheets are folded into a compact globule. The folding is driven by the non-specific hydrophobic interactions (the burial of hydrophobic residues from water), but the structure is stable only when the parts of a protein domain are locked into place by specific tertiary interactions, such as salt bridges, hydrogen bonds, and the tight packing of side chains and disulfide bonds. The disulfide bonds are extremely rare in cytosolic proteins, since the cytosol is generally a reducing environment.
Quaternary structure 
Quaternary structure is the three-dimensional structure of a multi-subunit protein and how the subunits fit together. In this context, the quaternary structure is stabilized by the same non-covalent interactions and disulfide bonds as the tertiary structure. Complexes of two or more polypeptides (i.e. multiple subunits) are called multimers. Specifically it would be called a dimer if it contains two subunits, a trimer if it contains three subunits, and a tetramer if it contains four subunits. The subunits are frequently related to one another by symmetry operations, such as a 2-fold axis in a dimer. Multimers made up of identical subunits are referred to with a prefix of "homo-" (e.g. a homotetramer) and those made up of different subunits are referred to with a prefix of "hetero-" (e.g. a heterotetramer, such as the two alpha and two beta chains of hemoglobin).
Domains, motifs, and folds in protein structure 
Protein are frequently described as consisting from several structural units.
- A structural domain is an element of the protein's overall structure that is self-stabilizing and often folds independently of the rest of the protein chain. Many domains are not unique to the protein products of one gene or one gene family but instead appear in a variety of proteins. Domains often are named and singled out because they figure prominently in the biological function of the protein they belong to; for example, the "calcium-binding domain of calmodulin". Because they are independently stable, domains can be "swapped" by genetic engineering between one protein and another to make chimeras.
- The structural and sequence motifs refer to short segments of protein three-dimensional structure or amino acid sequence that were found in a large number of different proteins.
- The supersecondary structure refers to a specific combination of secondary structure elements, such as beta-alpha-beta units or helix-turn-helix motif. Some of them may be also referred to as structural motifs.
- Protein fold refers to the general protein architecture, like helix bundle, beta-barrel, Rossman fold or different "folds" provided in the Structural Classification of Proteins database.
Despite the fact that there are about 100,000 different proteins expressed in eukaryotic systems, there are many fewer different domains, structural motifs and folds.
Protein folding 
Protein structure determination 
Around 90% of the protein structures available in the Protein Data Bank have been determined by X-ray crystallography. This method allows one to measure the 3D density distribution of electrons in the protein (in the crystallized state) and thereby infer the 3D coordinates of all the atoms to be determined to a certain resolution. Roughly 9% of the known protein structures have been obtained by Nuclear Magnetic Resonance techniques. The secondary structure composition can be determined via circular dichroism. Cryo-electron microscopy has recently become a means of determining protein structures to high resolution (less than 5 angstroms or 0.5 nanometer) and is anticipated to increase in power as a tool for high resolution work in the next decade. This technique is still a valuable resource for researchers working with very large protein complexes such as virus coat proteins and amyloid fibers. A more qualitative picture of protein structure is often obtained by proteolysis, which is also useful to screen for more crystallisable protein samples. Novel implementations of this approach (including Fast parallel proteolysis (FASTpp)) can probe the structured fraction and its stability without the need for purification.
Structure classification 
Computational prediction of protein structure 
The generation of a protein sequence is much easier than the determination of a protein structure. However, the structure of a protein gives much more insight in the function of the protein than its sequence. Therefore, a number of methods for the computational prediction of protein structure from its sequence have been developed. Ab initio prediction methods use just the sequence of the protein. Threading and Homology Modeling methods can build a 3D model for a protein of unknown structure from experimental structures of evolutionary related proteins.
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Further reading 
- 50 Years of Protein Structure Determination Timeline - HTML Version - National Institute of General Medical Sciences at NIH
- PDBWiki — A discussion forum for macromolecular structures (see PDBWiki)
- Proteopedia — Annotation of protein structures and other biomolecules
- TOPSAN — Annotation of protein structures in Structural genomics
- SSS Database — super-secondary structure protein database
- SPROUTS (Structural Prediction for pRotein fOlding UTility System)
- SMIR (Most Interacting Residues)