A simple method for mapping the location of cross-β-forming regions within protein domains of low sequence complexity

• 成果类型: Article
• 署名作者: Gu, Jinge; Zhou, Xiaoming; Sutherland, Lillian; Liszczak, Glen; Mcknight, Steven L.
• 署名单位: University of Texas System; University of Texas Southwestern Medical Center; Westlake University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12924
• DOI: 10.1073/pnas.2503382122
• 发表日期: 2025-04-29
• 关键词: intrinsically disordered regions; cell-free formation; phase-separation; rna-binding; lc domain; phosphorylation; hydrogel; polymers; droplets

摘要

Protein domains of low sequence complexity are unable to fold into stable, three-dimensional structures. In test tube studies, these unusual polypeptide regions can self-associate in a manner causing phase separation from aqueous solution. This form of protein:protein interaction has been implicated in numerous examples of dynamic morphological organization within eukaryotic cells. In several cases, the basis for low complexity domain (LCD) self-association and phase separation has been traced to the formation of labile cross-beta structures. The primary energetic force favoring formation of these transient and reversible structures is enabled by polypeptide backbone interactions. Short, contiguous networks of peptide backbone amino groups and carbonyl oxygens are zippered together intermolecularly by hydrogen bonding as described by Linus Pauling seven decades ago. Here, we describe a simple, molecular biological method useful for the identification of localized, self-associating regions within larger protein domains of low sequence complexity.