Evan Billings, Zixing Fan, Moloud Aflaki Sooreshjani, James C. Gumbart, Nicholas Noinaj
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引用次数: 0
Abstract
N. gonorrhoeae (Ngo) causes the sexually transmitted infection gonorrhea with ∼106 million infections worldwide annually. Ngo infections can result in an increased risk of acquiring HIV, infertility, and blindness. To combat Ngo infections, we report the cryoelectron microscopy (cryo-EM) structure of the Ngo β-barrel assembly machinery (NgBAM), which is responsible for the biogenesis of β-barrel outer membrane proteins (OMPs). NgBAM was observed in an inward-open state; however, the polypeptide transport-associated (POTRA) domains more closely match those found in the outward-open state in E. coli β-barrel assembly machinery (BAM). The barrel seam of NgBamA consists of partial pairing of strand β1 with β16; no outward-open state of NgBAM was observed. Molecular dynamics (MD) simulations reveal unique overall dynamics and interplay between the POTRA domains of NgBamA and NgBamD. We propose that in Ngo, initial recognition occurs in the inward-open state where the last strand of the OMP partially pairs with β1 of NgBamA and must compete off β16.
期刊介绍:
Structure aims to publish papers of exceptional interest in the field of structural biology. The journal strives to be essential reading for structural biologists, as well as biologists and biochemists that are interested in macromolecular structure and function. Structure strongly encourages the submission of manuscripts that present structural and molecular insights into biological function and mechanism. Other reports that address fundamental questions in structural biology, such as structure-based examinations of protein evolution, folding, and/or design, will also be considered. We will consider the application of any method, experimental or computational, at high or low resolution, to conduct structural investigations, as long as the method is appropriate for the biological, functional, and mechanistic question(s) being addressed. Likewise, reports describing single-molecule analysis of biological mechanisms are welcome.
In general, the editors encourage submission of experimental structural studies that are enriched by an analysis of structure-activity relationships and will not consider studies that solely report structural information unless the structure or analysis is of exceptional and broad interest. Studies reporting only homology models, de novo models, or molecular dynamics simulations are also discouraged unless the models are informed by or validated by novel experimental data; rationalization of a large body of existing experimental evidence and making testable predictions based on a model or simulation is often not considered sufficient.