The Nest is a type of protein structural motif. It is a small recurring anion-binding feature of both

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

s and

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

s. Each consists of the main chain atoms of three consecutive

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

residues. The main chain NH groups bind the anions while the side chain atoms are often not involved.

Proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...

residues lack NH groups so are rare in nests. About one in 12 of amino acid residues in proteins, on average, belongs to a nest.

Nest conformations

The conformation of a nest is such that the NH groups of the first and third amino acid residues are liable to be

hydrogen bond In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a ...

ed to a negatively charged, or partially negatively charged, atom, often an oxygen atom. The NH of the second residue may also be hydrogen bonded to the same atom but usually points somewhat away. These main chain atoms form a concavity called a nest into which an anionic atom fits. Such anionic atoms are sometimes called eggs and more than one egg may occur bound to a nest. The

oxyanion An oxyanion, or oxoanion, is an ion with the generic formula (where A represents a chemical element and O represents an oxygen atom). Oxyanions are formed by a large majority of the chemical elements. The formulae of simple oxyanions are determine ...

hole of the intestinal

serine protease Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site. They are found ubiquitously in both eukaryotes and prokaryotes. ...

s is a functional example of a nest. Another occurs at the bottom of a deep cavity in the

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

peptide

vancomycin Vancomycin is a glycopeptide antibiotic medication used to treat a number of bacterial infections. It is recommended intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, ...

which binds a key

carboxylate In organic chemistry, a carboxylate is the conjugate base of a carboxylic acid, (or ). It is an ion with negative charge. Carboxylate salts are salts that have the general formula , where M is a metal and ''n'' is 1, 2,...; ''carboxylat ...

group utilized during the final stages of

bacterial cell wall A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough, flexible, and sometimes rigid. It provides the cell with both structural support and protection, and also acts as a filtering mech ...

synthesis, thereby preventing bacterial cells from multiplying. Nests are defined by the conformation of the main chain atoms, namely the phi, psi

dihedral angle A dihedral angle is the angle between two intersecting planes or half-planes. In chemistry, it is the clockwise angle between half-planes through two sets of three atoms, having two atoms in common. In solid geometry, it is defined as the uni ...

s of the first two amino acids in the nest. For a typical (RL) nest phi_i=-90°; psi_i=0°; phi_i+1=80°; psi_i+1=20°. Nests vary in their degree of concavity. A few have so little that the concavity is lost; these peptides often bind cations via their main chain CO groups, instead of anions via their NH groups. The specificity filter of the

potassium channel Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cel ...

and the water channel of

aquaporin Aquaporins, also called water channels, are channel proteins from a larger family of major intrinsic proteins that form pores in the membrane of biological cells, mainly facilitating transport of water between cells. The cell membranes of a v ...

exhibit this more linear conformation in which

carbonyl group In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a ...

s are employed by proteins to transport molecules across membranes. This near-linear conformation is also that found in a strand of

alpha sheet Alpha sheet (also known as alpha pleated sheet or polar pleated sheet) is an atypical secondary structure in proteins, first proposed by Linus Pauling and Robert Corey in 1951.Pauling, L. & Corey, R. B. (1951). The pleated sheet, a new layer conf ...

Compound nests

If two nests overlap such that residue i+1 of the first nest is residue i of the second nest, a compound nest is formed. This has four NH groups instead of three. If three nests overlap such that residues i+1 and i+2 of the first nest are residue i of the second and third nest, a wider compound nest is formed with five NH groups, and so on. The main chain atoms form part of an incomplete ring with the NH groups all pointing roughly towards the centre of the ring. Because their concavities are often wider than simple nests, compound nests are commonly employed by proteins for binding multi-atom anions such as

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phospho ...

s, as in the

P-loop The Walker A and Walker B motifs are protein sequence motifs, known to have highly conserved three-dimensional structures. These were first reported in ATP-binding proteins by Walker and co-workers in 1982. Of the two motifs, the A motif is t ...

Walker motifs The Walker A and Walker B motifs are protein sequence motifs, known to have highly conserved three-dimensional structures. These were first reported in ATP-binding proteins by Walker and co-workers in 1982. Of the two motifs, the A motif is ...

, and in iron-sulphur clusters. The synthesized peptide Ser-Gly-Ala-Gly-Lys-Thr, designed as a minimal peptide

, was shown to bind inorganic phosphate strongly at neutral pH.

Types of nest

Simple nests are of two kinds called RL and LR depending on the sign of the phi angles of the first two nest residues. R residues have negative phi values (as in right-handed alpha-helices) and L residues have positive phi values (as in the left-handed

alpha helix The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues e ...

). Eighty percent of nests are RL and 20% are LR. When two nests overlap they may be RLR or LRL. When three nests overlap they may be RLRL or LRLR, and so on. Every

Schellman loop Schellman loops (also called Schellman motifs or paperclips) are commonly occurring structural features of proteins and polypeptides. Each has six amino acid residues (labelled residues ''i'' to ''i''+5) with two specific inter-mainchain hydrogen ...

incorporates an RL nest in the last three of its six residues. The nest binds

carbonyl In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a ...

oxygen atoms preceding it in sequence. A number of

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

proteins have RLR nests within the hairpin loops of their H-chain CDRs (

complementarity determining regions Complementarity-determining regions (CDRs) are part of the variable chains in immunoglobulins (antibodies) and T cell receptors, generated by B-cells and T-cells respectively, where these molecules bind to their specific antigen. A set of CDRs co ...

) bound to a carboxylate side chain. These have been engineered to give rise to monoclonal nest-containing antibodies specific for proteins with phosphorylated

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...

s and

threonine Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), a carboxyl group (which is in the deprotonated −COO� ...

s. Most

PDZ domain The PDZ domain is a common structural domain of 80-90 amino-acids found in the signaling proteins of bacteria, yeast, plants, viruses and animals. Proteins containing PDZ domains play a key role in anchoring receptor proteins in the membrane to ...

s have an RL nest at the beginning of the first beta-strand, with the function of recognizing the carboxylate group at the C-terminus of the domain's peptide or protein ligand.

References

External links

* Motivated Proteins:

* PDBeMotif

{{cite journal, last=Golovin, first=A, author2=Henrick, title=MSDmotif: exploring protein sites and motifs, journal=BMC Bioinformatics, year=2008, volume=9, pages=312, doi=10.1186/1471-2105-9-312, pmid=18637174, pmc=2491636, issue=1 Protein structural motifs Tripeptides