An Amino Acid Packing Code for 伪-Helical Structure and Protein Design

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• 作者：Hyun Joo^&dagger ; ; Archana G. Chavan^&dagger ; ; Jamie Phan ; Ryan Day ; Jerry Tsai ; ^{jtsai@pacific.edu}
• 关键词：RPC ; relative packing clique
• 刊名：Journal of Molecular Biology
• 出版年：2012
• 期刊代码：102_00222836
• 类别：imm
• 出版时间：8 June, 2012
• 卷：419
• 期：3-4
• 页码：234-254
• 文件大小：1805 K

摘要

This work demonstrates that all packing in 伪-helices can be simplified to repetitive patterns of a single motif: the knob-socket. Using the precision of Voronoi Polyhedra/Delauney Tessellations to identify contacts, the knob-socket is a four-residue tetrahedral motif: a knob residue on one 伪-helix packs into the three-residue socket on another 伪-helix. The principle of the knob-socket model relates the packing between levels of protein structure: the intra-helical packing arrangements within secondary structure that permit inter-helix tertiary packing interactions. Within an 伪-helix, the three-residue sockets arrange residues into a uniform packing lattice. Inter-helix packing results from a definable pattern of interdigitated knob-socket motifs between two 伪-helices. Furthermore, the knob-socket model classifies three types of sockets: (1) free, favoring only intra-helical packing; (2) filled, favoring inter-helical interactions; and (3) non, disfavoring 伪-helical structure. The amino acid propensities in these three socket classes essentially represent an amino acid code for structure in 伪-helical packing. Using this code, we used a novel yet straightforward approach for the design of 伪-helical structure to validate the knob-socket model. Unique sequences for three peptides were created to produce a predicted amount of 伪-helical structure: mostly helical, some helical, and no helix. These three peptides were synthesized, and helical content was assessed using CD spectroscopy. The measured 伪-helicity of each peptide was consistent with the expected predictions. These results and analysis demonstrate that the knob-socket motif functions as the basic unit of packing and presents an intuitive tool to decipher the rules governing packing in protein structure.