Hydrogen bonds with π-acceptors in proteins: frequencies and role in stabilizing local 3D structures11Edited by R. Huber

Crystallographic studies have suggested that the cysteine at position 67 (Cys67) in the B pocket of the MHC molecule HLA-B*2705 is of importance for peptide binding, and biophysical studies have documented altered thermodynamic stability of the molecule when Cys67 was mutated to serine (Ser67). In this study, we used HLA-B27.Cys67 and HLA-B27.Ser67 tetramers with defined T cell epitopes to determine the contribution of this polymorphic, solvent-inaccessible MHC residue to T cell recognition. We generated these HLA-B27 tetramers using immunodominant viral peptides with high binding affinity to HLA-B27 and cartilage-derived peptides with lower affinity. We demonstrate that the yield of refolding of HLA-B27.Ser67 molecules was higher than for HLA-B27.Cys67 molecules and strongly dependent on the affinity of the peptide. T cell recognition did not differ between HLA-B27.Cys67 and HLA.B27.Ser67 tetramers for the viral peptides that were investigated. However, an aggrecan peptide-specific T cell line derived from an HLA-B27 transgenic BALB/c mouse bound significantly stronger to the HLA-B27.Cys67 tetramer than to the HLA-B27.Ser67 tetramer. Modeling studies of the molecular structure suggest the loss of a SH … π hydrogen bond with the Cys→Ser substitution in the HLA-B27 H chain which reduces the stability of the HLA-B27/peptide complex. These results demonstrate that a solvent-inaccessible residue in the B pocket of HLA-B27 can affect TCR binding in a peptide-dependent fashion.

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“…. Ͻ 4.0 Å [3.5 Å]) (41). This type of hydrogen bond is rarely found and is suggested to be weaker than classical hydrogen bonds (41).…”

Section: Impact Of Cys 67 For the Coordination Of Pr2 In The B Pocketmentioning

confidence: 99%

The Solvent-Inaccessible Cys67 Residue of HLA-B27 Contributes to T Cell Recognition of HLA-B27/Peptide Complexes

Appel

Kuon

Kuhne

et al. 2004

The Journal of Immunology

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“…2 In addition, weaker donor groups such as Ca-H and methyl-H are also possible contributors to protein stability. [5][6][7][8][9] More specifically, other hydrogen-bond-like, NCIs have been implicated, including the n!p* interaction [10][11][12] and methyl-p interactions. 13,14 These particular interactions are much weaker than canonical hydrogen bonds: the latter are typically worth 3-10 kcal/ mol 15,16 ; whereas, n!p* interactions are estimated at 0.7-1.2 kcal/mol, 10,16 and methyl-p interactions at 0.9-1.5 kcal/mol.…”

Section: Introductionmentioning

confidence: 99%

On the satisfaction of backbone‐carbonyl lone pairs of electrons in protein structures

Bartlett

Woolfson

2016

Protein Science

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Protein structures are stabilized by a variety of noncovalent interactions (NCIs), including the hydrophobic effect, hydrogen bonds, electrostatic forces and van der Waals' interactions. Our knowledge of the contributions of NCIs, and the interplay between them remains incomplete. This has implications for computational modeling of NCIs, and our ability to understand and predict protein structure, stability, and function. One consideration is the satisfaction of the full potential for NCIs made by backbone atoms. Most commonly, backbone-carbonyl oxygen atoms located within a-helices and b-sheets are depicted as making a single hydrogen bond. However, there are two lone pairs of electrons to be satisfied for each of these atoms. To explore this, we used operational geometric definitions to generate an inventory of NCIs for backbone-carbonyl oxygen atoms from a set of high-resolution protein structures and associated molecular-dynamics simulations in water. We included more-recently appreciated, but weaker NCIs in our analysis, such as nfip* interactions, Ca-H bonds and methyl-H bonds. The data demonstrate balanced, dynamic systems for all proteins, with most backbone-carbonyl oxygen atoms being satisfied by two NCIs most of the time. Combinations of NCIs made may correlate with secondary structure type, though in subtly different ways from traditional models of a-and b-structure. In addition, we find examples of under-and over-satisfied carbonyl-oxygen atoms, and we identify both sequencedependent and sequence-independent secondary-structural motifs in which these reside. Our analysis provides a more-detailed understanding of these contributors to protein structure and stability, which will be of use in protein modeling, engineering and design.

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“…[21] X-H⋯π interactions have also been identified in proteins [19,22,23] and N-H⋯π interactions can be sufficiently strong to affect secondary (folding) structure. [24] Estimations of the strengths of X-H⋯π interactions have typically relied on the determination of the thermodynamics of complexation. This can be informative in the gas phase but in condensed phases, the difficulty of separating the intrinsic strength of the H-bonding interaction from the contribution of solvation energies to the stability constant has thwarted the development of useful scales of π basicity.…”

Section: Introductionmentioning

confidence: 99%

“…[31,32] Sometimes one of the acceptors of a bifurcated H-bond is an O-atom, the other an alkyne [19,33,34] or arene. [24,35] Bi-or multifurcated H-bonds are frequently deduced from protein crystallography. [36] The solution phase existence of compounds with bifurcated π-H bonds involving only unsaturated hydrocarbons has not been reported.…”

Section: Introductionmentioning

confidence: 99%

The Basicity of Unsaturated Hydrocarbons as Probed by Hydrogen‐Bond‐Acceptor Ability: Bifurcated NH⁺⋅⋅⋅π Hydrogen Bonding

Stoyanov

Stoyanova

Reed

2008

Chemistry A European J

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The competitive substitution of the anion in contact ion pairs of the type [Oct 3 NH + ]B(C 6 F 5 ) 4 − by unsaturated hydrocarbons L in accordance with the equilibrium Oct 3 NH + ⋯Anion − + nL ↔ [Oct 3 NH + ⋯L n ]Anion − has been studied in CCl 4 solution. On the basis of equilibrium constants K and shifts of νNH to low frequency, it is established that complexed Oct 3 NH + ⋯L n cations with n = 1 and 2 are formed, having unidentate and bifurcated N-H + ⋯π hydrogen bonds, respectively. Bifurcated H-bonds to unsaturated hydrocarbons have not been observed previously. The unsaturated hydro-carbons studied include benzene and methylbenzenes, fused-ring aromatics, alkenes, conjugated dienes, and alkynes. From the magnitude of the red shifts in N-H stretching frequencies, ΔνNH, a new scale for ranking the π-basicity of unsaturated hydrocarbons is proposed: fused-ring aromatics ≤ benzene < toluene < xylene < mesitylene < durene < conjugated dienes ∼ 1-alkynes < pentamethylbenzene < hexamethyl-benzene < internal alkynes ∼ cyclo-alkenes < 1-methylcycloalkenes. This scale is relevant to the discussion of π complexes for incipient protonation reactions and to understanding N-H + ⋯π hydrogen bonding in proteins and molecular crystals.

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Hydrogen bonds with π-acceptors in proteins: frequencies and role in stabilizing local 3D structures11Edited by R. Huber

Cited by 503 publications

References 67 publications

The Solvent-Inaccessible Cys67 Residue of HLA-B27 Contributes to T Cell Recognition of HLA-B27/Peptide Complexes

The Solvent-Inaccessible Cys67 Residue of HLA-B27 Contributes to T Cell Recognition of HLA-B27/Peptide Complexes

On the satisfaction of backbone‐carbonyl lone pairs of electrons in protein structures

The Basicity of Unsaturated Hydrocarbons as Probed by Hydrogen‐Bond‐Acceptor Ability: Bifurcated NH⁺⋅⋅⋅π Hydrogen Bonding

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Hydrogen bonds with π-acceptors in proteins: frequencies and role in stabilizing local 3D structures11Edited by R. Huber

Cited by 503 publications

References 67 publications

The Solvent-Inaccessible Cys67 Residue of HLA-B27 Contributes to T Cell Recognition of HLA-B27/Peptide Complexes

The Solvent-Inaccessible Cys67 Residue of HLA-B27 Contributes to T Cell Recognition of HLA-B27/Peptide Complexes

On the satisfaction of backbone‐carbonyl lone pairs of electrons in protein structures

The Basicity of Unsaturated Hydrocarbons as Probed by Hydrogen‐Bond‐Acceptor Ability: Bifurcated NH+⋅⋅⋅π Hydrogen Bonding

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Product

Resources

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The Basicity of Unsaturated Hydrocarbons as Probed by Hydrogen‐Bond‐Acceptor Ability: Bifurcated NH⁺⋅⋅⋅π Hydrogen Bonding