Residue-Specific Contact Order and Contact Breadth in Single-Domain Proteins: Implications for Folding as a Function of Chain Elongation

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• 作者：Nee Kurt ; Bryan C. Mounce ; Paul A. Ellison ; Silvia Cavagnero
• 刊名：Biotechnology Progress
• 出版年：2008
• 出版时间：June 2008
• 年：2008
• 卷：24
• 期：3
• 页码：570 - 575
• 全文大小：263K
• 年卷期：v.24,no.3(June 2008)
• ISSN：1520-6033

文摘

Cotranslational protein misfolding and aggregation are often responsible for inclusion bodyformation during in vivo protein expression. This study addresses the relations between proteinfolding/misfolding and the distribution of intramolecular interactions across different regions ofthe polypeptide chain in soluble single-domain proteins. The sequence regions examined hereinclude the C terminus, which is synthesized last in the cell. Emphasis is placed on two parametersreporting on short- and long-range interactions, i.e., residue-specific contact order (RCO) anda new descriptor of intramolecular protein interaction networks denoted as residue-specific contactbreadth (RCB). RCB illustrates the average spread in sequence of the residues serving asinteraction counterparts. We show that both RCO and RCB are maximized at the chain terminifor a large fraction of single-domain soluble proteins. A direct implication of this result is thatthe C terminus of the polypeptide chain, which is synthesized last during ribosome-assistedtranslation, plays a key role in the generation of native-like structure by establishing long-rangeinteractions and generating contacts with interaction counterparts widely distributed across thesequence. Comparison of our computational predictions with the experimental behavior of selectedproteins shows that the presence and absence of large RCO and RCB at the chain termini correlateswith the protein's ability to properly fold either after the C terminus has been synthesized orduring chain elongation, respectively.