Structure and mechanism for streptococcal fatty acid kinase (Fak) system dedicated to host fatty acid scavenging

• Published in: Science advances Vol. 8; no. 35; p. eabq3944
• Main Authors: Shi, Yu, Zang, Ning, Lou, Ningjie, Xu, Yongchang, Sun, Jingdu, Huang, Man, Zhang, Huimin, Lu, Huijie, Zhou, Chun, Feng, Youjun
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 02.09.2022
• Subjects: Biomedicine and Life Sciences; Life Sciences; SciAdv r-articles; Structural Biology
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.abq3944

and , two groups of major human pathogens, are equipped with a fatty acid kinase (Fak) machinery to scavenge host fatty acids. The Fak complex is contains an ATP-binding subunit FakA, which interacts with varied FakB isoforms, and synthesizes acyl-phosphate from extracellular fatty acids. However, how FakA recognizes its FakB partners and then activates different fatty acids is poorly understood. Here, we systematically describe the Fak system from the zoonotic pathogen, . The crystal structure of SsFakA complexed with SsFakB2 was determined at 2.6 Å resolution. An in vitro system of Fak-PlsX (phosphate: acyl-ACP transacylase) was developed to track acyl-phosphate intermediate and its final product acyl-ACP. Structure-guided mutagenesis enabled us to characterize a mechanism for streptococcal FakA working with FakB partners engaged in host fatty acid scavenging. These findings offer a comprehensive description of the Fak kinase machinery, thus advancing the discovery of attractive targets against deadly infections with .