Protein folding class

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The protein folding classes (English. Protein fold class ) describe broad categories of topologies of the tertiary structure of proteins . Any different topology could be viewed as a convolution . They describe groups of proteins with similar proportions of amino acids and secondary structures . Each class contains several independent protein superfamilies (i.e., are not necessarily evolutionarily related to one another).

Generally recognized classes

The two structure classification databases SCOP and CATH have agreed on four major protein folding classes.

all-α

All-α-proteins are a class of structural domains in which the secondary structure is entirely composed of α-helices , with the possible exception that some isolated β-sheets exist on the outer regions of the protein. This includes the following structural elements:

  • Simple helix : There are a number of examples of small proteins (or peptides ) made up of just a single helix. A notable example is glucagon , a hormone that is involved in regulating sugar metabolism in mammals (like insulin ).
  • Helix-turn-helix motif : The motif is a main structural motif that is ableto bind DNA . Each monomer contains two α-helices thatare linkedby a short strand of amino acids ( β-loop ) and bind to the main groove of the DNA. The HTH motif is found in many proteins thatregulate gene expression . This includes the homeodomain folding system
  • Helix bundle : A helix bundle is a small protein fold that consists of several α-helices that are usually nearly parallel or antiparallel to each other. One example is the bromodomain .
  • Globin fold : The globin fold typically consists of eight α-helices, although some proteins have additional helix extensions at their termini. One example is myoglobin .
  • α-Selenoid : The α-selenoid is a protein fold made up of repeating α-helix subunits, usually helix-turn-helix motifs, which are arranged antiparallel to form a superhelix. One example is protein phosphatase 2A .

all-β

All-β proteins are a class of structural domains in which the secondary structure consists entirely of β sheets, with the possible exception of a few isolated α-helices on the outer regions. This includes the following structural elements:

  • β sandwich : protein domain with at least two opposing (antiparallel) β strands and at least one β loop. One example is the immunoglobulin folding.
  • β-barrel : It consists of at least five β-pleated sheets that are arranged in a circle and thus form a tube (the pore), which is mostly responsible for the protein's function as a transport protein. One example is the SH3 domain .
  • β-propeller : A β-propeller is a kind of all-β-protein architecture, which is characterized by 4 to 8 highly symmetrical β-sheets, whichare arranged toroidally around a central axis (like the blades of a propeller). Together the β-sheets form a funnel-like active center. One example is the neuraminidase of the influenza virus .
  • β trefoil fold : The β trefoil fold is a protein fold that consists of six β hairpins , each made up of two β strands. One example is the interleukin-1 family.
  • β-Helix : The β-helix is ​​a structural motif with tandem repetition, which is formed by the association of parallel β-strands in a helical pattern with two or three sides. One example is pectate lyase from Aspergillus niger .

α + β

Alpha + beta proteins are a class of structural domains in which the secondary structure consists of alpha helices and beta strands that appear separately along the backbone . The β strands are therefore mostly anti-parallel. Examples are ribonuclease A and the SH2 domain . The structural elements include:

  • DNA clamp : The DNA chamber is an α + β protein that assembles into a multimeric structure that completely surrounds the DNA double helix when the polymerase adds nucleotides to the growing strand. The DNA clamp isassembledon the DNA at the replication fork and “slides” along the DNA with the advancing polymerase, supported by a layer of water molecules in the central pore of the clamp between the DNA and the protein surface. One example is the proliferating cell nuclear antigen .
  • Ferredoxin fold : The ferredoxin fold can be viewed as a long, symmetrical hairpin that is wrapped once so that its two terminal β-strands hydrogen bond to the central two β-strands and form a four-stranded, anti-parallel β-sheet , which is covered on one side by two α-helices. One example is acyl phosphatase .

α / β

Alpha / beta proteins are a class of structural domains in which the secondary structure consists of alternating alpha helices and beta strands along the backbone. The β strands are therefore mostly parallel. This includes the following structural elements:

  • Rossmann fold : This fold consists of alternating β-strands and α-helix segments, whereby the β-strandsare hydrogen-bonded to form an extended β-sheetand the α-helices surround both sides of the sheet to form a three-layer "sandwich" to manufacture. One example is L-lactate dehydrogenase .
  • α / β-horseshoe : Typically, each repeat unit has a β-strand - loop - α-helix structure, and the composite domain consisting of many such repeats has a horseshoe shape with an inner parallel β-pleated sheet layer and an outer arrangement of α -Helices. One example is the leucine-rich repeat .
  • α / β-barrel : In an α / β-barrel the α-helices and β-strands form a kind of “cylinder coil ”, which bends in the form of a donut, which is topologically referred to as a toroid , and thus closes itself. The parallel β-strands form the inner wall of the "donut", while the α-helices form the outer wall of the "donut". One example is the TIM barrel .
  • Flavodoxin fold : The flavodoxin fold consists of three layers, with two α-helical layers enclosing a 5-strand parallel β-sheet. Examples of this are flavoproteins .
  • Thioredoxin fold : The thioredoxin fold consists of a four-stranded antiparallel β-sheet which is arranged between three α-helices. An example of this is DNAJC10 .

Additional classes

Membrane proteins

Membrane proteins interact with biomembranes either by being integrated or by being bound via a covalently bound lipid . Along with soluble globular proteins , fibrillar proteins, and disordered proteins, they are one of the most common types of proteins. They are targets of over 50% of all modern medicines. It is estimated that 20-30% of all genes in most genomes encode membrane proteins.

Intrinsically Disordered Proteins

Intrinsically disordered proteins (IDP) do not have a fixed or ordered three-dimensional structure. IDPs cover a spectrum of states, from completely unstructured to partially structured, and include random coils , (pre-) molten globules, and large multi-domain proteins linked by flexible linkers. They form one of the main types of proteins (besides globular, fibrillar and membrane proteins).

Coiled coils

Coiled coils form long, insoluble fibers that participate in the extracellular matrix . A coiled coil is a structural motif in proteins in which 2–7 α-helices are wound together like strands of a rope (dimers and trimers are the most common types). Many coiled-coil proteins are involved in important biological functions such as the regulation of gene expression , e.g. B. Transcription Factors .

Small proteins

Small proteins typically have a tertiary structure that is maintained by disulfide bridges (cysteine-rich proteins), metal ligands (metal-binding proteins), and / or cofactors such as heme .

Designed proteins

Designed proteins 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 of a known protein structure and its sequence (known as protein redesign). Rational protein design approaches make predictions about protein sequences that will fold into specific structures. These predicted sequences can then be validated experimentally using methods such as peptide synthesis , site-specific mutagenesis, or artificial gene synthesis .

Web links

Individual evidence

  1. ↑ John Walshaw, Alan Mills: Protein Folds. In: bbk.ac.uk. Birkbeck, University of London, April 1995, accessed October 30, 2019 .
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  3. ↑ LH Greene, TE Lewis, S. Addou, A. Cuff, T. Dallman, M. Dibley, O. Redfern, F. Pearl, R. Nambudiry, A. Reid, I. Sillitoe, C. Yeats, JM Thornton, CA Orengo: The CATH domain structure database: new protocols and classification levels give a more comprehensive resource for exploring evolution. In: Nucleic acids research. Volume 35, Database issue January 2007, pp. D291 – D297, doi : 10.1093 / nar / gkl959 , PMID 17135200 , PMC 1751535 (free full text).
  4. ↑ a b A. V. Efimov: Structural similarity between two-layer alpha / beta and beta-proteins. In: Journal of molecular biology. Volume 245, Number 4, January 1995, pp. 402-415, doi : 10.1006 / jmbi.1994.0033 , PMID 7837272 (review).
  5. ^ I. Bruck, M. O'Donnell: The ring-type polymerase sliding clamp family. In: Genome biology. Volume 2, number 1, 2001, S. REVIEWS3001, doi : 10.1186 / gb-2001-2-1-reviews3001 , PMID 11178284 , PMC 150441 (free full text) (review).
  6. ^ A b A. Andreeva, D. Howorth, C. Chothia, E. Kulesha, AG Murzin: SCOP2 prototype: a new approach to protein structure mining. In: Nucleic acids research. Volume 42, Database issue January 2014, pp. D310 – D314, doi : 10.1093 / nar / gkt1242 , PMID 24293656 , PMC 3964979 (free full text).
  7. ↑ JP Overington, as Al-Lazikani, AL Hopkins: How many drug targets are there? In: Nature reviews. Drug discovery. Volume 5, Number 12, December 2006, pp. 993-996, doi : 10.1038 / nrd2199 , PMID 17139284 (review).
  8. ↑ AK Dunker, JD Lawson, CJ Brown, RM Williams, P. Romero, JS Oh, CJ Oldfield, AM Campen, CM Ratliff, KW Hipps, J. Ausio, MS Nissen, R. Reeves, C. Kang, CR Kissinger, RW Bailey, MD Griswold, W. Chiu, EC Garner, Z. Obradovic: Intrinsically disordered protein. In: Journal of molecular graphics & modeling. Volume 19, Number 1, 2001, pp. 26-59, PMID 11381529 (review).
  9. ^ HJ Dyson, PE Wright: Intrinsically unstructured proteins and their functions. In: Nature reviews. Molecular cell biology. Volume 6, Number 3, March 2005, pp. 197-208, doi : 10.1038 / nrm1589 , PMID 15738986 (review).
  10. ↑ J. Liu, Q. Zheng, Y. Deng, CS Cheng, NR Kallenbach, M. Lu: A seven-helix coiled coil. In: Proceedings of the National Academy of Sciences . Volume 103, number 42, October 2006, pp. 15457-15462, doi : 10.1073 / pnas.0604871103 , PMID 17030805 , PMC 1622844 (free full text).