A conserved strategy to attack collagen: The activator domain in bacterial collagenases unwinds triple- helical collagen

• 成果类型: Article
• 署名作者: Serwanja, Jamil; Wieland, Alexander C.; Haubenhofer, Astrid; Brandstetter, Hans; Schoenauer, Esther
• 署名单位: Salzburg University; Salzburg University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13495
• DOI: 10.1073/pnas.2321002121
• 发表日期: 2024-04-16
• 关键词: structural basis; conformation; mechanism; reveals

摘要

Bacterial collagenases are important virulence factors, secreted by several pathogenic Clostridium, Bacillus, Spirochaetes, and Vibrio species. Yet, the mechanism by which these enzymes cleave collagen is not well understood. Based on biochemical and mutational studies we reveal that collagenase G (ColG) from Hathewaya histolytica recognizes and processes collagen substrates differently depending on their nature (fibrillar vs. soluble collagen); distinct dynamic interactions between the activator and peptidase domain are required based on the substrate type. Using biochemical and circular dichroism studies, we identify the presumed noncatalytic activator domain as the single- domain triple helicase that unwinds collagen locally, transiently, and reversibly.