Position-specific propensities of amino acids in the β-strand

BMC Structural Biology, Sep 2010

Background Despite the importance of β-strands as main building blocks in proteins, the propensity of amino acid in β-strands is not well-understood as it has been more difficult to determine experimentally compared to α-helices. Recent studies have shown that most of the amino acids have significantly high or low propensity towards both ends of β-strands. However, a comprehensive analysis of the sequence dependent amino acid propensities at positions between the ends of the β-strand has not been investigated. Results The propensities of the amino acids calculated from a large non-redundant database of proteins are found to be highly position-specific and vary continuously throughout the length of the β-strand. They follow an unexpected characteristic periodic pattern in inner positions with respect to the cap residues in both termini of β-strands; this periodic nature is markedly different from that of the α-helices with respect to the strength and pattern in periodicity. This periodicity is not only different for different amino acids but it also varies considerably for the amino acids belonging to the same physico-chemical group. Average hydrophobicity is also found to be periodic with respect to the positions from both termini of β-strands. Conclusions The results contradict the earlier perception of isotropic nature of amino acid propensities in the middle region of β-strands. These position-specific propensities should be of immense help in understanding the factors responsible for β-strand design and efficient prediction of β-strand structure in unknown proteins.

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Position-specific propensities of amino acids in the β-strand

BMC Structural Biology Position-specific propensities of amino acids in the b-strand Nicholus Bhattacharjee 0 Parbati Biswas 0 0 Department of Chemistry, University of Delhi , Delhi - 110007 , India Background: Despite the importance of b-strands as main building blocks in proteins, the propensity of amino acid in b-strands is not well-understood as it has been more difficult to determine experimentally compared to a-helices. Recent studies have shown that most of the amino acids have significantly high or low propensity towards both ends of b-strands. However, a comprehensive analysis of the sequence dependent amino acid propensities at positions between the ends of the b-strand has not been investigated. Results: The propensities of the amino acids calculated from a large non-redundant database of proteins are found to be highly position-specific and vary continuously throughout the length of the b-strand. They follow an unexpected characteristic periodic pattern in inner positions with respect to the cap residues in both termini of b-strands; this periodic nature is markedly different from that of the a-helices with respect to the strength and pattern in periodicity. This periodicity is not only different for different amino acids but it also varies considerably for the amino acids belonging to the same physico-chemical group. Average hydrophobicity is also found to be periodic with respect to the positions from both termini of b-strands. Conclusions: The results contradict the earlier perception of isotropic nature of amino acid propensities in the middle region of b-strands. These position-specific propensities should be of immense help in understanding the factors responsible for b-strand design and efficient prediction of b-strand structure in unknown proteins. - Background Secondary structural elements like a-helices and b-strands are important determinants of folded protein structure and topology. Helices and strands are regular repetitive structures; while a-helices are quasi-onedimensional formed by local interactions [1,2], long b-strands self-assemble into complex hydrogen-bonded b-sheets by long-range and inter-chain interactions [3-5]. Secondary structures are predicted on the basis of statistical analysis of known protein structures, fold recognition and multiple sequence alignments. Various close packing arrangements of these strands and helices are systematically optimized [6] to test the resultant tertiary structure or a specific fold. It is, therefore, important to understand the factors dictating the intrinsic preferences of amino acid residues for a particular secondary structure [7]. Statistical analysis of known proteins [7,8] clearly reveals that amino acids have definite conformational preferences for one or the other type of secondary structure. Secondary structure prediction methods [9-13] systematically analyze how these preferences determine whether a given sequence will adopt an a-helical or a b-sheet topology or neither. Even the frequencies of occurrences of amino acid residues in a helix at the N-terminus end (N-cap), at the C-terminus end (C-cap) and at interior positions are very different [14-25]. This non-equivalence of different positions around the helix termini with respect to amino acid preferences is also supported by experimental results [26-36]. Though early studies establish distinct differences in the propensities of the amino acids at N-cap, N1, N2 and N3 positions [14,15,37-39], it was assumed that beyond the first few residues from both the termini, the individual propensities average out leading to essentially isotropic environments [16]. An unexpected recent finding confirms that the sequence dependence of helical propensities at positions between the ends of helices are markedly different and they exhibit a distinct pattern throughout the helix length [40]. Despite the importance of b-strands as main building blocks in proteins, the propensity of b-strands is not well-understood as it has been more difficult to determine experimentally compared to a-helices. This is attributed to the fact that b-sheets do not fold independently. Another reason may be the structural context dependence of the amino acids in b-sheet formation. A statistical survey of the protein structure database correlates well with an average of the experimental scales to determine the b-sheet propensity [41] and supports the idea that the intrinsic b-sheet propensity plays a pivotal role in assessing protein stability [42]. Various factors like the side-chain dependent steric interactions [43] and solvent screening of the backbone electrostatic interactions [44] dictate the preference of the amino acids for b-sheet formation. Conformational entropy analysis also quantitatively establishes [45] the role of steric clashes between the side-chain and local backbone of an amino acid as the dominant cause of intrinsic b-sheet propensity. Recently, it has been proved that even the confo (...truncated)


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Nicholus Bhattacharjee, Parbati Biswas. Position-specific propensities of amino acids in the β-strand, BMC Structural Biology, 2010, pp. 29, 10, DOI: 10.1186/1472-6807-10-29