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4mze

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4mze, resolution 1.80Å ()
Ligands: , , , , , , , ,
Gene: HN (Human parainfluenza 3 virus (strain NIH 47885))
Activity: Exo-alpha-sialidase, with EC number 3.2.1.18
Related: 4mza


Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

Crystal structure of hPIV3 hemagglutinin-neuraminidase, H552Q/Q559R mutant

Publication Abstract from PubMed

ABSTRACT Paramyxoviruses, enveloped RNA viruses that include human parainfluenza virus type 3 (HPIV3), cause the majority of childhood viral pneumonia. HPIV3 infection starts when the viral receptor-binding protein engages sialic acid receptors in the lung and the viral envelope fuses with the target cell membrane. Fusion/entry requires interaction between two viral surface glycoproteins: tetrameric hemagglutinin-neuraminidase (HN) and fusion protein (F). In this report, we define structural correlates of the HN features that permit infection in vivo. We have shown that viruses with an HN-F that promotes growth in cultured immortalized cells are impaired in differentiated human airway epithelial cell cultures (HAE) and in vivo and evolve in HAE into viable viruses with less fusogenic HN-F. In this report, we identify specific structural features of the HN dimer interface that modulate HN-F interaction and fusion triggering and directly impact infection. Crystal structures of HN, which promotes viral growth in vivo, show a diminished interface in the HN dimer compared to the reference strain's HN, consistent with biochemical and biological data indicating decreased dimerization and decreased interaction with F protein. The crystallographic data suggest a structural explanation for the HN's altered ability to activate F and reveal properties that are critical for infection in vivo. IMPORTANCE Human parainfluenza viruses cause the majority of childhood cases of croup, bronchiolitis, and pneumonia worldwide. Enveloped viruses must fuse their membranes with the target cell membranes in order to initiate infection. Parainfluenza fusion proceeds via a multistep reaction orchestrated by the two glycoproteins that make up its fusion machine. In vivo, viruses adapt for survival by evolving to acquire a set of fusion machinery features that provide key clues about requirements for infection in human beings. Infection of the lung by parainfluenzavirus is determined by specific interactions between the receptor binding molecule (hemagglutinin-neuraminidase [HN]) and the fusion protein (F). Here we identify specific structural features of the HN dimer interface that modulate HN-F interaction and fusion and directly impact infection. The crystallographic and biochemical data point to a structural explanation for the HN's altered ability to activate F for fusion and reveal properties that are critical for infection by this important lung virus in vivo.

Interaction between the Hemagglutinin-Neuraminidase and Fusion Glycoproteins of Human Parainfluenza Virus Type III Regulates Viral Growth In Vivo., Xu R, Palmer SG, Porotto M, Palermo LM, Niewiesk S, Wilson IA, Moscona A, MBio. 2013 Oct 22;4(5). pii: e00803-13. doi: 10.1128/mBio.00803-13. PMID:24149514

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Function

[HN_PI3H4] Attaches the virus to sialic acid-containing cell receptors and thereby initiating infection. Binding of HN protein to the receptor induces a conformational change that allows the F protein to trigger virion/cell membranes fusion (By similarity). Neuraminidase activity ensures the efficient spread of the virus by dissociating the mature virions from the neuraminic acid containing glycoproteins (By similarity).

About this Structure

4mze is a 2 chain structure with sequence from Human parainfluenza 3 virus (strain nih 47885). Full crystallographic information is available from OCA.

Reference

  • Xu R, Palmer SG, Porotto M, Palermo LM, Niewiesk S, Wilson IA, Moscona A. Interaction between the Hemagglutinin-Neuraminidase and Fusion Glycoproteins of Human Parainfluenza Virus Type III Regulates Viral Growth In Vivo. MBio. 2013 Oct 22;4(5). pii: e00803-13. doi: 10.1128/mBio.00803-13. PMID:24149514 doi:http://dx.doi.org/10.1128/mBio.00803-13

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