Comparative analysis of 13C chemical shifts of β-sheet amyloid proteins and outer membrane proteins

• Published in: Journal of biomolecular NMR Vol. 75; no. 4-5; pp. 151 - 166
• Main Authors: Somberg, Noah H., Gelenter, Martin D., Hong, Mei
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-05-2021; Springer Nature B.V
• Subjects: Amino acids; Barrels; Biochemistry; Biological and Medical Physics; Biophysics; Comparative analysis; Fibrils; Hydrophobicity; Lipids; Membrane proteins; Membranes; NMR; Nuclear magnetic resonance; Outer membrane proteins; Physics; Physics and Astronomy; Proteins; Residues; Spectroscopy/Spectrometry; Structural analysis; Trends; Chemical shifts; Conformational distribution; Amyloid proteins; Beta-barrel membrane proteins
• ISSN: 0925-2738; 1573-5001
• DOI: 10.1007/s10858-021-00364-y

Cross-β amyloid fibrils and membrane-bound β-barrels are two important classes of β-sheet proteins. To investigate whether there are systematic differences in the backbone and sidechain conformations of these two families of proteins, here we analyze the
13
C chemical shifts of 17 amyloid proteins and 7 β-barrel membrane proteins whose high-resolution structures have been determined by NMR. These 24 proteins contain 373 β-sheet residues in amyloid fibrils and 521 β-sheet residues in β-barrel membrane proteins. The
13
C chemical shifts are shown in 2D
13
C–
13
C correlation maps, and the amino acid residues are categorized by two criteria: (1) whether they occur in β-strand segments or in loops and turns; (2) whether they are water-exposed or dry, facing other residues or lipids. We also examine the abundance of each amino acid in amyloid proteins and β-barrels and compare the sidechain rotameric populations. The
13
C chemical shifts indicate that hydrophobic methyl-rich residues and aromatic residues exhibit larger static sidechain conformational disorder in amyloid fibrils than in β-barrels. In comparison, hydroxyl- and amide-containing polar residues have more ordered sidechains and more ordered backbones in amyloid fibrils than in β-barrels. These trends can be explained by steric zipper interactions between β-sheet planes in cross-β fibrils, and by the interactions of β-barrel residues with lipid and water in the membrane. These conformational trends should be useful for structural analysis of amyloid fibrils and β-barrels based principally on NMR chemical shifts.