Sandbox Reserved 816

This Sandbox is Reserved from 06/12/2018, through 30/06/2019 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1480 through Sandbox Reserved 1543.

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spinqualitylabelsall models Internalin K bound to MVP Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

IntroductionIntroduction

Internalin K is a protein from Listeria monocytogene which is a Gram-positive bacterium human pathogen. Its the ability to survive in the human intestine and to cross a variety of membranes, including mucosal, intestinal, placental, and blood–brain barriers, allows it to generate illnesses ranging from gastroenteritis in healthy individuals to bacteremia and meningitis in immunocompromised patients, as well as mother-to-child infections.These pathologies are caused by the unusual capacity of the bacterium to cross three host barriers during infection and to invade nonphagocytic cells. Listeria monocytogene can survive in a variety of cell types and proteins of the internalin family have been shown to play a key role in this survival

Internalin K is involved in Listeria monocytogene ability to escape from autophagy by recruitment of to the bacterial surface.

StructureStructure

Internalin family's generalitiesInternalin family's generalities

L.monocytogenes uses a lot of virulence factors to initiate infection. Proteins of the internalin's family, virulence factors, plays a key role in the infection's survival in a variety of cell types. They play key roles in processes ranging from adhesion to receptor recognition and there are essential for infection. The internalin family uses a binding partner action.

The three-dimensional structure of the internalin family shows that there are modular proteins in order to improve the link with the partner. A common architecture is pointed, the N-terminal domain, also called N-terminal leucine-rich repeats (LRRs). It is composed of 22-residue regions including a β-strand and an helix. The structure is a curved solenoid. LRR is followed by domains in cell signaling and often in bacterial surface attachment. Whereas the C-terminal regions are not similar that contributes the variety of roles. Each internalin plays a specific role in the infection.

Internalin family

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Structural comparison of the regions that follow the LRR domains in Internalin K (yellow) shows that Internalin K has a more complex fold.

Structure of Internalin KStructure of Internalin K

Internalin K is a multi-domain virulence factor. It harbours four domains formed in the shape of "bent arm".

Domains and are related to domains and by an 90° angle.

The domain composed of a two-helical cap region and also by the leucine-rich repeats (LRRs). It is stably associated to .

has few contacts with which improves the flexibility required by Internalin K to bind to its partner while remaining associated to the surface of the bacterium.

The association of and domains represent the "elbow" region. It means the recognition of domain.

Domains and , located in tandem and related to each other by an approximate 2-fold axis, both fold into compact structures composed of three antiparallel strands packed against two small helices. There are immunoglobulin-like domain.

and are involved in binding to protein partners while and most probably serve as pedestals. The flexibility between domains of its elongated structure may play a key role in this complex function.

Function of internalin KFunction of internalin K

Interaction Internalin K-major vault proteinInteraction Internalin K-major vault protein

The surface-associated Internalin K with Major Vault Protein escapes to ubiquitination and autophagic recognition processes. It means that the recruitment of major vault protein avoids autophagy. MVP is the largest cytoplasmic ribonucleoprotein particle known and is higly abundant in the cytoplasm of eukaryotic cell. The interaction between Internalin K and MVP could be facilitated by internalin K's notable structural flexibility. This flexibility is essential for binding. It plays a key role in pathogen intracellular mobility and infection.

Function of internalin K in Listeria monocytogenesFunction of internalin K in Listeria monocytogenes

Internalin K is the first internalin identified as being important for concealment of the pathogen from the eukaryotic defense system rather than cellular entry. The flexible structure permits concealment from recognition by molecules involved in the autophagy process. Internalin K has a key role in Listeria monocytogenes infection, it is involved in the survival of the Gram-positive bacterium by avoided its destruction.

ReferencesReferences

1. David Neves1,Viviana Job,Laurent Dortet,Pascale Cossart,Andréa Dessen,Structure of Internalin InlK from the Human Pathogen Listeria monocytogenes, J Mol Biol (2013). http://dx.doi.org/10.1016/j.jmb.2013.08.010

2. Matteo Bonazzi,Marc Lecuit,Pascale Cossart,Listeria monocytogenes Internalin and E-cadherin: From Bench to Bedside. Cold Spring Harb Perspect Biol. 2009 October.PMCID: PMC2773623 doi: 10.1101/cshperspect.a003087

External RessourcesExternal Ressources

http://www.rcsb.org/pdb/explore/explore.do?structureId=4L3F

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773623/

Protreopedia Page Contributors and EditorsProtreopedia Page Contributors and Editors

Lecomte Alix

Karasiewicz Tania

Student 1A ESBS (Promo 2016)