Beta sheet 4906 222141072 2008-06-27T19:23:17Z Quadell 57108 Converting [1] to <ref>, and/or misc fixes using [[Project:AutoWikiBrowser|AWB]] [[Image:BetaPleatedSheetProtein.png|right|thumb|200px|Diagram of β-pleated sheet with H-bonding between protein strands]] The '''β sheet''' (also '''β-pleated sheet''') is the second form of regular [[secondary structure]] in [[protein]]s consisting of '''beta strands''' connected laterally by three or more [[hydrogen bond]]s, forming a generally twisted, pleated sheet (the most common form of regular secondary structure in proteins is the [[alpha helix]]). A beta strand (also '''β-strand''') is a stretch of [[amino acid]]s typically 5–10 amino acids long whose peptide backbones are almost fully extended. The association of beta sheets has been implicated in the formation of protein aggregates and fibrils observed in many human diseases, notably the [[amyloidosis| amyloidoses]]. ==Nomenclature== In the most common usage, ''β strand'' refers to a single continuous stretch of amino acids adopting an extended conformation and involved in [[hydrogen bond]]s; by contrast, a ''β sheet'' refers to an ''assembly'' of such strands that are [[hydrogen bond|hydrogen-bonded]] to each other. ==History== The first β sheet structure was proposed by [[William Astbury]] in the 1930s. He proposed the idea of hydrogen bonding between the [[peptide bond]]s of parallel or antiparallel extended β strands. However, Astbury did not have the necessary data on the bond geometry of the amino acids in order to build accurate models, especially since he did not then know that the [[peptide bond]] was planar. A refined version was proposed by [[Linus Pauling]] and [[Robert Corey]] in 1951. ==Structure and orientation== {| align=right | [[Image:Beta sheet bonding antiparallel-color.svg|right|thumb|Illustration of the [[hydrogen bonding]] patterns, represented by dotted lines, in an '''antiparallel''' beta sheet. [[Oxygen]] atoms are colored red and [[nitrogen]] atoms colored blue.]] || [[Image:Beta sheet bonding parallel-color.svg|thumb|right|thumb|Illustration of the [[hydrogen bonding]] patterns, represented by dotted lines, in a '''parallel''' beta sheet. [[Oxygen]] atoms are colored red and [[nitrogen]] atoms colored blue.]] |} ===Geometry=== The majority of β strands are arranged adjacent to other strands and form an extensive [[hydrogen bond]] network with their neighbors in which the [[amine|N-H]] groups in the backbone of one strand establish [[hydrogen bond]]s with the [[carbonyl|C=O]] groups in the backbone of the adjacent strands. In the fully extended β strand, successive side chains point straight up, then straight down, then straight up, etc. Adjacent β strands in a β sheet are aligned so that their C<sup>α</sup> atoms are adjacent and their side chains point in the same direction. The "pleated" appearance of β strands arises from tetrahedral chemical bonding at the C<sup>α</sup> atom; for example, if a side chain points straight up, then the bond to the <math>\mathrm{C^{\prime}}</math> must point slightly downwards, since its bond angle is approximately 109.5°. The pleating causes the distance between <math>\mathrm{C^{\alpha}}_{i}</math> and <math>\mathrm{C^{\alpha}_{i+2}}</math> to be approximately 6 [[ångström|Å]], rather than the 7.6 Å (2 × 3.8 Å) expected from two fully extended [[trans]] [[peptide bond|peptide]] [[virtual bond]]s. The "sideways" distance between adjacent C<sup>α</sup> atoms in [[hydrogen bond|hydrogen-bonded]] β strands is roughly 5 Å. However, β strands are rarely perfectly extended; rather, they exhibit a slight twist due to the [[chirality (chemistry)|chirality]] of their component amino acids. The energetically preferred [[dihedral angle]]s (φ, ψ) = (–135°, 135°) (broadly, the upper left region of the [[Ramachandran plot]]) diverge somewhat from the fully extended conformation (φ, ψ) = (–180°, 180°).<ref>Voet D, Voet JG. (2004). Biochemistry Vol 1 3rd ed. Wiley. See esp. pp 227–231.</ref> The twist is often associated with alternating fluctuations in the [[dihedral angle]]s to prevent the individual β strands in a larger sheet from splaying apart. A good example of such a twisted β-hairpin can be seen in the protein [[BPTI]]. The side chains point outwards from the folds of the pleats, roughly perpendicularly to the plane of the sheet; successive residues point outwards on alternating faces of the sheet. ===Hydrogen bonding patterns=== Because peptide chains have a directionality conferred by their [[N-terminal end|N-terminus]] and [[C-terminal end|C-terminus]], β strands too can be said to be directional. They are usually represented in protein topology diagrams by an arrow pointing toward the C-terminus. Adjacent β strands can form [[hydrogen bond]]s in antiparallel, parallel, or mixed arrangements. In an antiparallel arrangement, the successive β strands alternate directions so that the N-terminus of one strand is adjacent to the C-terminus of the next. This is the arrangement that produces the strongest inter-strand stability because it allows the inter-strand hydrogen bonds between carbonyls and amines to be planar, which is their preferred orientation. The peptide backbone dihedral angles (φ, ψ) are about (–140°, 135°) in antiparallel sheets. In this case, if two atoms <math>\mathrm{C^{\alpha}_{i}}</math> and <math>\mathrm{C^{\alpha}_{j}}</math> are adjacent in two [[hydrogen bond|hydrogen-bonded]] β strands, then they form two mutual backbone hydrogen bonds to each other's flanking [[peptide bond|peptide groups]]; this is known as a '''close pair''' of hydrogen bonds. In a parallel arrangement, all of the N-termini of successive strands are oriented in the same direction; this orientation is slightly less stable because it introduces nonplanarity in the inter-strand hydrogen bonding pattern. The dihedral angles (φ, ψ) are about (–120°, 115°) in parallel sheets. It is rare to find less than five interacting parallel strands in a motif, suggesting that a smaller number of strands may be unstable. In this case, if two atoms <math>\mathrm{C^{\alpha}_{i}}</math> and <math>\mathrm{C^{\alpha}_{j}}</math> are adjacent in two [[hydrogen bond|hydrogen-bonded]] β strands, then they do ''not'' hydrogen bond to each other; rather, one residue forms hydrogen bonds to the residues that flank the other (but not vice versa). For example, residue <math>i</math> may form hydrogen bonds to residues <math>j-1</math> and <math>j+1</math>; this is known as a ''wide pair'' of hydrogen bonds. By contrast, residue <math>j</math> may hydrogen-bond to different residues altogether, or to none at all. Finally, an individual strand may exhibit a mixed bonding pattern, with a parallel strand on one side and an antiparallel strand on the other. Such arrangements are less common than a random distribution of orientations would suggest, indicating that this pattern is less stable than the antiparallel arrangement. The [[hydrogen bond]]ing of β strands need not be perfect, but can exhibit localized disruptions known as [[beta bulge]]s. The hydrogen bonds lie roughly in the plane of the sheet, with the [[peptide bond|peptide]] [[carbonyl]] groups pointing in alternating directions with successive residues; for comparison, successive carbonyls point in the ''same'' direction in the [[alpha helix]]. ===Amino acid propensities=== Large aromatic residues (Tyr, Phe and Trp) and β-branched amino acids (Thr, Val, Ile) are favored to be found in β strands in the ''middle'' of β sheets. Interestingly, different types of residues (such as Pro) are likely to be found in the ''edge'' strands in β sheets, presumably to avoid the "edge-to-edge" association between proteins that might lead to [[aggregation]] and [[amyloid]] formation. ==Common structural motifs== [[Image:beta-meander1.png|right|325px|thumb|<div align="center">'''Beta-meander motif'''<br/>Portion of outer surface Protein A of [[Borrelia burgdorferi]] complexed with a murine [[monoclonal antibodies|monoclonal antibody]].<br/></div>]] [[Image:Beta hairpin.png|thumb|left|Representation of a [[beta hairpin]]]] A very simple [[structural motif]] involving β sheets is the [[beta hairpin|β hairpin]], in which two antiparallel strands are linked by a short loop of two to five residues, of which one is frequently a [[glycine]] or a [[proline]], both of which can assume the unusual dihedral-angle conformations required for a tight [[turn (biochemistry)|turn]]. However, individual strands can also be linked in more elaborate ways with long loops that may contain [[alpha helix|alpha helices]] or even entire protein domains. ===Greek key motif=== The [[Greek key]] motif consists of four adjacent antiparallel strands and their linking loops. It consists of three antiparallel strands connected by hairpins, while the fourth is adjacent to the first and linked to the third by a longer loop. This type of structure forms easily during the protein folding process. It was named after a pattern common to Greek ornamental artwork. ===The β-&alpha;-β motif=== Due to the chirality of their component amino acids, all strands exhibit a "right-handed" twist evident in most higher-order β sheet structures. In particular, the linking loop between two parallel strands almost always has a right-handed crossover chirality, which is strongly favored by the inherent twist of the sheet. This linking loop frequently contains a helical region, in which case it is called a [[beta-alpha-beta|β-&alpha;-β]] motif. A closely related motif called a β-α-β-α motif forms the basic component of the most common protein [[tertiary structure]], the [[TIM barrel]]. [[Image:5CPAgood.png|right|thumb|<div align="center">'''Psi-loop motif'''<br/>Portion of [[Carboxypeptidase A]].<br/></div>]] ===β-meander motif=== A simple [[structural motif|supersecondary]] protein topology composed of 2 or more consecutive antiparallel β-strands linked together by [[beta hairpin|hairpin]] loops<ref>http://scop.mrc-lmb.cam.ac.uk/scop/data/scop.b.c.bbf.html</ref><ref>http://www.cryst.bbk.ac.uk/PPS2/course/section9/sss/super2.html</ref>. This motif is common in β-sheets and can be found in several structural architectures including [[beta barrel|β-barrels]] and [[beta propeller|β-propellers]]. ===Psi-loop motif=== The psi-loop, Ψ-loop, motif consists of two antiparallel strands with one strand in between that is connected to both by hydrogen bonds.<ref>Hutchinson E. & Thornton J. 1996, "Promotif-A program to identify and analyze structural motifs in proteins", ''Protein Science'', vol. 5, pp. 212-220.</ref> There are four possible strand topologies for single Ψ-loops as cited by Hutchinson ''et al.'' 1990. This motif is rare as the process resulting in its formation seems unlikely to occur during protein folding. The Ψ-loop was first identified in the [[aspartic acid protease|aspartic protease]] family.<ref>Hutchinson E. & Thornton J. 1990, "HERA-A program to draw schematic diagrams of protein secondary structures", ''Proteins: Structure, Function, and Genetics'', vol. 8, pp. 203-212.</ref> ==Structural architectures of proteins with beta-sheets== Beta-sheets are present in [[All-β proteins|all-β]], [[Α+β proteins|α+β]] and [[Α/β proteins|α/β]] domains according to [http://scop.mrc-lmb.cam.ac.uk/scop/ Structural Classification of Proteins] and in many [[peptide]]s or small proteins with poorly defined overal architecture. [[All-β proteins|All-β domains]] may form [[beta barrel|β barrels]], [[beta sandwich|β sandwiches]], [[beta prism|β prisms]], [[Beta-propeller domain|β propellers]], and [[Beta helix|β-helices]]. ==Structural topology== The '''topology''' of a β sheet describes the order of [[hydrogen bond|hydrogen-bonded]] β strands along the backbone. For example, the [[flavodoxin fold]] has a five-stranded, parallel β sheet with topology 21345; thus, the edge strands are β strand 2 and β strand 5 along the backbone. Spelled out explicitly, β strand 2 is H-bonded to β strand 1, which is H-bonded to β strand 3, which is H-bonded to β strand 4, which is H-bonded to β strand 5, the other edge strand. In the same system, the Greek key motif described above has a 4123 topology. The [[secondary structure]] of a β sheet can be described roughly by giving the number of strands, their topology, and whether their [[hydrogen bond]]s are parallel or antiparallel. β sheets can be ''open'', meaning that they have two edge strands (as in the [[flavodoxin fold]] or the [[immunoglobulin fold]])) or they can be ''closed [[beta-barrel|beta barrel]]s'' (such as the [[TIM barrel]]). [[beta-barrel|β-Barrels]] are often described by their ''stagger'' or ''shear''. Some open β sheets are very curved and fold over on themselves (as in the [[SH3 domain]]) or form horseshoe shapes (as in the [[ribonuclease inhibitor]]). Open β sheets can assemble face-to-face (such as the [[beta-propeller domain]] or [[immunoglobulin fold]]) or edge-to-edge, forming one big β sheet. ==Parallel β helices== A [[beta helix|β helix]] is formed from repeating structural units consisting of two or three short β strands linked by short loops. These units "stack" atop one another in a helical fashion so that successive repetitions of the same strand hydrogen-bond with each other in a parallel orientation. In [[beta helix|β helices]], the strands themselves are nearly planar; the resulting helical surfaces are nearly flat, forming a [[triangular prism]] shape. The two-strand helix is found in the enzyme pectate lyase. Its two loops are each six residues long and bind stabilizing calcium ions to maintain the integrity of the structure. The more complex three-strand helix contains three linking loops, of which one is consistently two residues long and the others are variable. This structure is found in bacteriophage P22 tailspike protein.<ref>Carl Branden and John Tooze. 1999. Introduction to Protein Structure 2nd ed. Garland Publishing: New York, NY. See esp. pp 20-32 and ch. 5.</ref> ==β sheets in pathology== Some proteins that are disordered or helical as monomers, such as amyloid β (see [[amyloid plaque]]) can form β-sheet-rich oligomeric structures associated with pathological states. The amyloid β protein's oligomeric form is implicated as a cause of [[Alzheimer's disease|Alzheimer's]]. Its structure has yet to be determined in full, but recent data suggests that it may resemble an unusual two-strand β helix.<ref>Nelson R, Sawaya MR, Balbirnie M, Madsen AO, Riekel C, Grothe R, Eisenberg D. 2005. Structure of the cross-beta spine of amyloid-like fibrils. ''Nature'' 435: 773-8.</ref> The side chains from the amino acid residues found in a β sheet structure may also be arranged such that many of the adjacent sidechains on one side of the sheet are hydrophobic, while many of those adjacent to each other on the alternate side of the sheet are polar or charged (hydrophilic), which can be useful if the sheet is to form a boundary between polar/watery and nonpolar/greasy environments. ==References== {{reflist}} *Cooper, J. [http://www.cryst.bbk.ac.uk/PPS2/course/section9/sss/super2.html "Super Secondary Structure - Part II"], [[May 31]],[[1996]]. Accessed [[May 25]],[[2007]]. *Structural Classification of Proteins (SCOP) [http://scop.mrc-lmb.cam.ac.uk/scop/data/scop.b.c.bbf.html "Open-sided Beta-meander"], [[October 20]], [[2006]]. Accessed [[May 31]], [[2007]]. ==See also== *[[Folding (chemistry)]] *[[Tertiary structure]] *[[Alpha helix|&alpha; helix]] *[[Collagen helix]] *[[Foldamers]] ==External links== *[http://www2.ufp.pt/~pedros/anim/2frame_sheeten.htm Interactive model of an anti-parallel β sheet] (plug-in required) *[http://www2.ufp.pt/~pedros/anim/2frame_psheeten.htm Interactive model of a parallel β sheet] (plug-in required) *[http://www3.interscience.wiley.com:8100/legacy/college/voet/047119350X/animated_figures/html/8-16.html Animated details of β-pleated sheet] {{Protein secondary structure}} [[Category:Protein structural motifs]] [[de:Β-Faltblatt]] [[es:Beta-lámina]] [[fr:Feuillet bêta]] [[he:משטח בטא]] [[lt:Beta klostės]] [[nl:Bèta-sheet]] [[ja:Βシート]] [[pl:Harmonijka beta]] [[pt:Folha-beta]] [[sr:Бета раван]] [[fi:Beeta-levy]] [[sv:Betaflak]] [[uk:Бета-лист]] [[zh:Β摺疊]]