Structural basis for adhesin secretion by the outer-membrane usher in type 1 pili
Ryan M Bitter1, Maxwell I Zimmerman2,3, Brock T Summers4
1Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, MO 63110.
Summary
Gram-negative bacteria use chaperone-usher pili for host interaction. This study reveals how the adhesin FimH changes shape to translocate through the usher pore, crucial for pilus assembly and infections.
Area of Science:
- Microbiology
- Structural Biology
- Biochemistry
Background:
- Chaperone-usher pathway pili are critical virulence factors in Gram-negative bacteria.
- These pili mediate host-pathogen interactions and tissue tropism through specific adhesin binding.
- The mechanism of adhesin translocation across the outer membrane via the usher pore is not fully understood.
Purpose of the Study:
- To elucidate the structural mechanisms of adhesin translocation through the outer membrane usher.
- To investigate the role of structural plasticity in pilus biogenesis and function.
- To provide molecular insights into FimH and usher dynamics relevant to urinary tract infections.
Main Methods:
- Cryoelectron microscopy (cryo-EM) to determine the structure of a quaternary tip complex (FimD, FimC, FimH, FimF).
- Biochemical assays, including piliation assays, to assess the functional significance of structural findings.
- Comparative structural analysis of different states of the adhesin during translocation.
Main Results:
- A cryo-EM structure captured the usher FimD secreting the adhesin FimH, revealing a unique intermediate state.
- The two-domain adhesin FimH exhibits significant structural plasticity during translocation.
- A flexible linker between FimH domains enables this plasticity, which is essential for usher translocation and pilus assembly.
Conclusions:
- Structural plasticity of the adhesin is a prerequisite for translocation through the usher pore.
- This study provides unprecedented molecular details of adhesin secretion across the outer membrane.
- Understanding these dynamics is critical for developing novel therapeutics against Gram-negative bacterial infections, including urinary tract infections.
Related Concept Videos
01:24Adherens Junctions
4.7K
Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types – adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic
Adherens Junctions are Dynamic
4.7K
01:39Mechanism of Filopodia Formation
2.3K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.3K
01:29Cytoskeletal Proteins in Bacteria
3.3K
Bacterial cells were initially considered simple, randomly organized structures lacking a cytoskeleton. However, the discovery of cytoskeleton homologs in bacteria led to the change of this opinion. Bacterial cytoskeletal filaments regulate the cell shape, cell polarity, cell division, and partitioning of plasmids during cell division. It was later discovered that bacterial cytoskeletal proteins, mainly actin and tubulin homologs, are diverse compared to their eukaryotic counterparts. On the...
3.3K
01:17Intracellular Signaling Affects Focal Adhesions
2.6K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.6K
01:03Anchoring Junctions
3.7K
Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
3.7K
01:25Structure of Cadherins
3.3K
The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins” is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This...
3.3K