Common Ring Motifs in Proteins Involving Asparagine or Glutamine Amide Groups Hydrogen-bonded to Main-chain Atoms

Questel, Jean‐Yves Le; Morris, David G.; Maccallum, Peter H.; Poet, Ron; Milner‐White, E. James

doi:10.1006/jmbi.1993.1335

Cited by 16 publications

(9 citation statements)

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“…Similar hydrogen bond interactions are observed in other protein structures (27). The mean and SD of the O/q' angles observed for residues whose main-chain atoms form hydrogen bonds to amide side chains were calculated, using the data from refined protein structures found in table 4 of Le Questel et al (27). The mean angles calculated from 32 examples from proteins in the Protein Data Bank for both the 9-and 11-membered ring motifs are similar, with overall averages of (4) = -93°+ 250 and (qi) = 1340 ± 15°.…”

Section: Resultssupporting

confidence: 85%

“…Of these, six are bidentate hydrogen bonds involving DR1 asparagines (a62, a69, and ,B82), which form 9-(,B82) and 11-membered (a62, a69) ring structures between the peptide main-chain atoms and the DR1 amide side-chain atoms. Similar hydrogen bond interactions are observed in other protein structures (27). The mean and SD of the O/q' angles observed for residues whose main-chain atoms form hydrogen bonds to amide side chains were calculated, using the data from refined protein structures found in table 4 of Le Questel et al (27).…”

Section: Resultsmentioning

confidence: 80%

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Crystallographic analysis of endogenous peptides associated with HLA-DR1 suggests a common, polyproline II-like conformation for bound peptides.

Jardetzky

Brown

Gorga

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

235

150

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The structure of the human major histocompatibility complex (MHC) class II molecule HLA-DR1 derived from the human lymphoblastoid cell line LG-2 has been determined in a complex with the Staphylococcus aureus enterotoxin B superantigen. The HLA-DR1 molecule contains a mixture of endogenous peptides derived from cellular or serum proteins bound in the antigen-binding site, which copurify with the class II molecule. Continuous electron density for 13 amino acid residues is observed in the MHC peptide-binding site, suggesting that this is the core length of peptide that forms common interactions with the MHC molecule. Electron density is also observed for side chains of the endogenous peptides. The electron density corresponding to peptide side chains that interact with the DR1-binding site is more clearly defined than the electron density that extends out of the binding site. The regions of the endogenous peptides that interact with DR1 are therefore either more restricted in conformation or sequence than the peptide side chains or amino acids that project out of the peptide-binding site. The hydrogen-bond interactions and conformation of a peptide model built into the electron density are similar to other HLA-DR-peptide structures. The bound peptides assume a regular conformation that is similar to a polyproline type II helix. The side-chain pockets and conserved asparagine residues of the DR1 molecule are well-positioned to interact with peptides in the polyproline type II conformation and may restrict the range of acceptable peptide conformations.Major histocompatibility complex (MHC) class II molecules present peptide antigens to T cells in the generation of an immune response (1). Antigenic peptides are derived from exogenous proteins, which are processed into peptide fragments by antigen-presenting cells. MHC class II molecules also bind self-peptides derived from cellularly produced proteins. Self-peptides isolated from purified class II molecules, including HLA-DR1 (2, 3), vary in length from -13 to 25 amino acids. This length variability contrasts with the shorter peptides found associated with MHC class I molecules, which are generally 9-11 amino acids long (4-6). For MHC class I molecules the N and C termini of peptides are typically bound in pockets at each end of the peptide-binding site (7-9), whereas for the MHC class II molecules, HLA-DR1 and HLA-DR3, peptides are free to extend out both ends of the binding site. Instead of the network of hydrogen bonds found between the MHC class I molecule and the peptide N and C termini, class II has evolved an alternative hydrogen-bondingThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.interaction along the length of the peptide main chain (10, 11), allowing the termini to extend out of the binding site. This hydrogen-bonding scheme provides interactions with mainchain atoms, which are present in...

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Section: Resultssupporting

confidence: 85%

Section: Resultsmentioning

confidence: 80%

Crystallographic analysis of endogenous peptides associated with HLA-DR1 suggests a common, polyproline II-like conformation for bound peptides.

Jardetzky

Brown

Gorga

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

235

150

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“…The Bigelow scale is no longer used; it contains a number of errors and omissions, including an unusually high hydrophobicity for the Pro residue compared with the more widely accepted value, close to that of the hydrophilic residue His, in the scale of Kyte and Doolittle (1982). Proline is not classified as a hydrophobic residue; it is seldom found in the core of globular proteins (Macarthur and Thornton, 1991;Le Questel et al, 1993) or in clusters of hydrophobic residues (Arunachalam and Gautham, 2008), partly because of the restricted range of Ramachandran angles accessible to imino acids and partly because the backbone carbonyl moiety is an excellent H-bond acceptor, making the residue more hydrophilic than its hydrophobicity would suggest, even on the scale of Kyte and Doolittle (1982). Likewise, the side chain of Gln can act as an H-bond acceptor and donor so the energetic cost of desolvating Gln is high.…”

Section: Quaternary Structures and The Hydrophobic Effectmentioning

confidence: 99%

“…Likewise, the side chain of Gln can act as an H-bond acceptor and donor so the energetic cost of desolvating Gln is high. It too is rarely found in the core of globular proteins (Le Questel et al, 1993). A nice illustration of the hydrophilicity of Pro is that Pro-rich oligomers tend to be quite soluble in aqueous solvents (Léonil et al, 1994).…”

Section: Quaternary Structures and The Hydrophobic Effectmentioning

confidence: 99%

Invited review: Caseins and the casein micelle: Their biological functions, structures, and behavior in foods

Holt

Carver

Ecroyd

et al. 2013

Journal of Dairy Science

393

240

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A typical casein micelle contains thousands of casein molecules, most of which form thermodynamically stable complexes with nanoclusters of amorphous calcium phosphate. Like many other unfolded proteins, caseins have an actual or potential tendency to assemble into toxic amyloid fibrils, particularly at the high concentrations found in milk. Fibrils do not form in milk because an alternative aggregation pathway is followed that results in formation of the casein micelle. As a result of forming micelles, nutritious milk can be secreted and stored without causing either pathological calcification or amyloidosis of the mother's mammary tissue. The ability to sequester nanoclusters of amorphous calcium phosphate in a stable complex is not unique to caseins. It has been demonstrated using a number of noncasein secreted phosphoproteins and may be of general physiological importance in preventing calcification of other biofluids and soft tissues. Thus, competent noncasein phosphoproteins have similar patterns of phosphorylation and the same type of flexible, unfolded conformation as caseins. The ability to suppress amyloid fibril formation by forming an alternative amorphous aggregate is also not unique to caseins and underlies the action of molecular chaperones such as the small heat-shock proteins. The open structure of the protein matrix of casein micelles is fragile and easily perturbed by changes in its environment. Perturbations can cause the polypeptide chains to segregate into regions of greater and lesser density. As a result, the reliable determination of the native structure of casein micelles continues to be extremely challenging. The biological functions of caseins, such as their chaperone activity, are determined by their composition and flexible conformation and by how the casein polypeptide chains interact with each other. These same properties determine how caseins behave in the manufacture of many dairy products and how they can be used as functional ingredients in other foods. aBStraCtA typical casein micelle contains thousands of casein molecules, most of which form thermodynamically stable complexes with nanoclusters of amorphous calcium phosphate. Like many other unfolded proteins, caseins have an actual or potential tendency to assemble into toxic amyloid fibrils, particularly at the high concentrations found in milk. Fibrils do not form in milk because an alternative aggregation pathway is followed that results in formation of the casein micelle. As a result of forming micelles, nutritious milk can be secreted and stored without causing either pathological calcification or amyloidosis of the mother's mammary tissue. The ability to sequester nanoclusters of amorphous calcium phosphate in a stable complex is not unique to caseins. It has been demonstrated using a number of noncasein secreted phosphoproteins and may be of general physiological importance in preventing calcification of other biofluids and soft tissues. Thus, competent noncasein phosphoproteins have similar patterns of phosp...

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“…This 20‐residue repeat (hereafter referred to as the PNNP repeat) is intriguing for two reasons. First, only two types of amino acids are utilized: Asn represents a putative site for side‐chain hydrogen bonding,16 and Pro represents a putative site for hydrophobic interaction 3. Second, the SM50 PNNP repeat is homologous to the NN‐rich repeats found in the aragonite‐specific protein nacrein,17 and to the PXP and PXXP repeats of the aragonite‐specific protein, Lustrin A 18.…”

Section: Introductionmentioning

confidence: 99%

Model peptide studies of sequence repeats derived from the intracrystalline biomineralization protein, SM50. II. Pro,Asn-Rich tandem repeats

Zhang

Evans

2000

Biopolymers

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In the biomineralization process, a number of Pro‐rich proteins participate in the formation of three‐dimensional supramolecular structures. One such protein superfamily, the Pro,Gly‐rich sea urchin intracrystalline spicule matrix proteins, form protein–protein supramolecular assemblies that modify the microstructure of the inorganic mineral phase (calcite) within embryonic sea urchin spicules and adult sea urchin spines. These proteins represent a useful model for understanding Pro sequence usage and the resulting generation of extended or “open” structures for protein–protein and/or protein–crystal recognition. In the sea urchin spicule matrix protein, SM50 (Strongylocentrotus purpuratus), there exists an unusual 20‐residue Pro,Asn‐containing repeat, PNNPNNPNPNNPNNPNNPNP, which links the upstream 15‐residue C‐terminal domain and the downstream 211‐residue β‐spiral repeat domain. To define the structural preferences of this 20‐residue repeat, we created a 20‐residue N‐ and C‐terminal “capped” peptidomimetic of this sequence. Using far‐uv CD dichroism, CHα and α‐15N conformational shifts, 3JNH‐CHα coupling constants, sequential dNN(i, i + 1) rotating frame nuclear Overhauser effect connectivities, dαN(i, i + 1)/dNN(i, i + 1) intensity ratios, amide temperature shift coefficients, amide solvent exchange, and simulated annealing refinement protocols, we have determined that this 20‐residue repeat motif adopts an extended “twist” structure consisting of turn‐ and coil‐like regions. These findings are consistent with previous studies, which have shown that Pro‐rich tandem repeats adopt extended, flexible structures in solution. We hypothesize that this 20‐residue repeat may fulfill the role of a mineral‐binding domain, a protein–protein docking domain, or as an internal “molecular spacer” for the SM50 protein during spicule biocomposite formation. © 2000 John Wiley & Sons, Inc. Biopoly 54: 464–475, 2000

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Common Ring Motifs in Proteins Involving Asparagine or Glutamine Amide Groups Hydrogen-bonded to Main-chain Atoms

Cited by 16 publications

References 0 publications

Crystallographic analysis of endogenous peptides associated with HLA-DR1 suggests a common, polyproline II-like conformation for bound peptides.

Crystallographic analysis of endogenous peptides associated with HLA-DR1 suggests a common, polyproline II-like conformation for bound peptides.

Invited review: Caseins and the casein micelle: Their biological functions, structures, and behavior in foods

Model peptide studies of sequence repeats derived from the intracrystalline biomineralization protein, SM50. II. Pro,Asn-Rich tandem repeats

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