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Literature detail

Mapping of the Lassa virus LAMP1 binding site reveals unique determinants not shared by other old world arenaviruses.

Hadar Israeli1 Hadas Cohen-Dvashi1 Anastasiya Shulman1 Amir Shimon1 Ron Diskin1
Affiliations 1 institutions
  1. Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
PMID 28448640 2017 PLoS Pathog eng epublish
PubMed DOI Browse context

Article

Publication summary

Cell entry of many enveloped viruses occurs by engagement with cellular receptors, followed by internalization into endocytic compartments and pH-induced membrane fusion. A previously unnoticed step of receptor switching was found to be critical during cell entry of two devastating human pathogens: Ebola and Lassa viruses. Our recent studies revealed the functional role of receptor switching to LAMP1 for triggering membrane fusion by Lassa virus and showed the involvement of conserved histidines in this switching, suggesting that other viruses from this family may also switch to LAMP1. However, when we investigated viruses that are genetically close to Lassa virus, we discovered that they cannot bind LAMP1. A crystal structure of the receptor-binding module from Morogoro virus revealed structural differences that allowed mapping of the LAMP1 binding site to a unique set of Lassa residues not shared by other viruses in its family, illustrating a key difference in the cell-entry mechanism of Lassa virus that may contribute to its pathogenicity.

Amino Acid Sequence Animals Arenaviridae Infections Arenaviruses, Old World Binding Sites Humans Lassa Fever Lassa virus Lysosomal Membrane Proteins Lysosomal-Associated Membrane Protein 1 Membrane Fusion Models, Molecular Models, Structural Protein Binding Receptors, Cell Surface Sequence Alignment Species Specificity LAMP1 protein, human

Structured evidence records

Evidence records

2 total
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.85
Key finding

Lassa virus possesses unique amino acid residues that enable binding to the host receptor LAMP1, unlike related Old World arenaviruses, revealing a molecular adaptation in its cell-entry and pathogenicity mechanism.

Virus
LASV
Host
Not specified
Location
Not specified
Supporting text

A crystal structure of the receptor-binding module from Morogoro virus revealed structural differences that allowed mapping of the LAMP1 binding site to a unique set of Lassa residues not shared by other viruses in its family, illustrating a key difference in the cell-entry mechanism of Lassa virus that may contribute to its pathogenicity.

Genes or proteins
receptor-binding module
Receptors
LAMP1
Mechanism types
receptor_binding; cell_entry; pathogenicity
Receptor Usage 1 records
Receptor Usage Extraction confidence 0.98
Key finding

Lassa virus binds the receptor LAMP1 to mediate membrane fusion, a receptor usage mechanism not shared by other Old World arenaviruses such as Morogoro virus.

Virus
LASV
Host
Not specified
Location
Not specified
Supporting text

Our recent studies revealed the functional role of receptor switching to LAMP1 for triggering membrane fusion by Lassa virus ... we discovered that they cannot bind LAMP1.

Method
structural analysis; crystal structure
Receptors
LAMP1