A summary of functional annotation of the most ancestral translation protein folds

In molecular biology, protein fold classes are broad categories of protein tertiary structure topology. They describe groups of proteins that share similar amino acid and

secondary structure Protein secondary structure is the three dimensional conformational isomerism, form of ''local segments'' of proteins. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...

proportions. Each class contains multiple, independent

protein superfamilies A protein superfamily is the largest grouping (clade) of proteins for which common ancestry can be inferred (see homology). Usually this common ancestry is inferred from structural alignment and mechanistic similarity, even if no sequence similari ...

(i.e. are not necessarily evolutionarily related to one another).

Generally recognised classes

Four large classes of protein that are generally agreed upon by the two main structure classification databases ( SCOP and

CATH The CATH Protein Structure Classification database is a free, publicly available online resource that provides information on the evolutionary relationships of protein domains. It was created in the mid-1990s by Professor Christine Orengo and coll ...

all-α

All-α proteins are a class of structural domains in which the

is composed entirely of α-helices, with the possible exception of a few isolated

β-sheets The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gen ...

on the periphery. Common examples include the

bromodomain A bromodomain is an approximately 110 amino acid protein domain that recognizes acetylated lysine residues, such as those on the ''N''-terminal tails of histones. Bromodomains, as the "readers" of lysine acetylation, are responsible in transducin ...

, the globin fold and the homeodomain fold.

all-β

All-β proteins are a class of structural domains in which the

is composed entirely of

, with the possible exception of a few isolated α-helices on the periphery. Common examples include the SH3 domain, the beta-propeller domain, the

immunoglobulin fold The immunoglobulin domain, also known as the immunoglobulin fold, is a type of protein domain that consists of a 2-layer sandwich of 7-9 antiparallel β-strands arranged in two β-sheets with a Greek key topology, consisting of about 125 amino ac ...

and

B3 DNA binding domain The B3 DNA binding domain (DBD) is a highly conserved domain found exclusively in transcription factors (≥40 species) () combined with other domains (). It consists of 100-120 residues, includes seven beta strands and two alpha helices that fo ...

α+β

α+β proteins are a class of structural domains in which the

is composed of α-helices and β-strands that occur separately along the backbone. The β-strands are therefore mostly ''antiparallel''. Common examples include the ferredoxin fold, ribonuclease A, and the SH2 domain.

α/β

α/β proteins are a class of structural domains in which the

is composed of alternating α-helices and β-strands along the backbone. The β-strands are therefore mostly ''parallel''. Common examples include the flavodoxin fold, the TIM barrel and leucine-rich-repeat (LRR) proteins such as ribonuclease inhibitor.

Additional classes

Membrane proteins

Membrane proteins interact with

biological membrane A biological membrane, biomembrane or cell membrane is a selectively permeable membrane that separates the interior of a cell from the external environment or creates intracellular compartments by serving as a boundary between one part of the ce ...

s either by inserting into it, or being tethered via a covalently attached lipid. They are one of the common types of protein along with soluble globular proteins,

fibrous proteins In molecular biology, fibrous proteins or scleroproteins are one of the three main classifications of protein structure (alongside globular and membrane proteins). Fibrous proteins are made up of elongated or fibrous polypeptide chains which fo ...

, and

disordered protein In molecular biology, an intrinsically disordered protein (IDP) is a protein that lacks a fixed or ordered protein tertiary structure, three-dimensional structure, typically in the absence of its macromolecular interaction partners, such as other ...

s. They are targets of over 50% of all modern medicinal drugs. It is estimated that 20–30% of all genes in most genomes encode membrane proteins.

Intrinsically disordered proteins

Intrinsically disordered protein In molecular biology, an intrinsically disordered protein (IDP) is a protein that lacks a fixed or ordered three-dimensional structure, typically in the absence of its macromolecular interaction partners, such as other proteins or RNA. IDPs rang ...

s lack a fixed or ordered three-dimensional structure. IDPs cover a spectrum of states from fully unstructured to partially structured and include random coils, (pre-)

molten globule In molecular biology, the term molten globule (MG) refers to protein states that are more or less compact (hence the "globule"), but are lacking the specific tight packing of amino acid residues which creates the solid state-like tertiary structu ...

s, and large multi-domain proteins connected by flexible linkers. They constitute one of the main types of protein (alongside globular, fibrous and membrane proteins).

Coiled coil proteins

Coiled coil proteins form long, insoluble

fibers Fiber or fibre (from la, fibra, links=no) is a natural or artificial substance that is significantly longer than it is wide. Fibers are often used in the manufacture of other materials. The strongest engineering materials often incorporate ...

involved in the extracellular matrix. There are many scleroprotein superfamilies including keratin,

collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...

elastin Elastin is a protein that in humans is encoded by the ''ELN'' gene. Elastin is a key component of the extracellular matrix in gnathostomes (jawed vertebrates). It is highly elastic and present in connective tissue allowing many tissues in the bod ...

, and fibroin. The roles of such proteins include protection and support, forming

connective tissue Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...

, tendons, bone matrices, and muscle fiber.

Small proteins

Small proteins typically have a tertiary structure that is maintained by

disulphide bridges In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...

( cysteine-rich proteins), metal ligands ( metal-binding proteins), and or

cofactors Cofactor may also refer to: * Cofactor (biochemistry), a substance that needs to be present in addition to an enzyme for a certain reaction to be catalysed * A domain parameter in elliptic curve cryptography, defined as the ratio between the order ...

such as heme.

Designed proteins

Numerous protein structures are the result of rational design and do not exist in nature. Proteins can be designed from scratch (''de novo'' design) or by making calculated variations on a known protein structure and its sequence (known as ''protein redesign''). Rational protein design approaches make protein-sequence predictions that will fold to specific structures. These predicted sequences can then be validated experimentally through methods such as peptide synthesis, site-directed mutagenesis, or Artificial gene synthesis.

References

{{reflist Protein folds