Structural Insights into the Anti-HIV Activity of the Oscillatoria agardhii Agglutinin Homolog Lectin Family

Leonardus M.I Koharudin,Sireesha Kollipara,Christopher Aiken,Angela M Gronenborn

doi:10.1074/jbc.m112.388579

Leonardus M.I Koharudin, Sireesha Kollipara + Show 2 more

Open Access

https://doi.org/10.1074/jbc.m112.388579

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Abstract

Oscillatoria agardhii agglutinin homolog (OAAH) proteins belong to a recently discovered lectin family. All members contain a sequence repeat of ~66 amino acids, with the number of repeats varying among different family members. Apart from data for the founding member OAA, neither three-dimensional structures, information about carbohydrate binding specificities, nor antiviral activity data have been available up to now for any other members of the OAAH family. To elucidate the structural basis for the antiviral mechanism of OAAHs, we determined the crystal structures of Pseudomonas fluorescens and Myxococcus xanthus lectins. Both proteins exhibit the same fold, resembling the founding family member, OAA, with minor differences in loop conformations. Carbohydrate binding studies by NMR and x-ray structures of glycan-lectin complexes reveal that the number of sugar binding sites corresponds to the number of sequence repeats in each protein. As for OAA, tight and specific binding to α3,α6-mannopentaose was observed. All the OAAH proteins described here exhibit potent anti-HIV activity at comparable levels. Altogether, our results provide structural details of the protein-carbohydrate interaction for this novel lectin family and insights into the molecular basis of their HIV inactivation properties.

Highlights

The Oscillatoria agardhii agglutinin homolog (OAAH) proteins constitute a novel lectin family
In an effort to characterize as many possible mannose-targeting lectins structurally, as well as with respect to their recognition epitopes, we recently investigated a novel antiviral lectin from the cyanobacterium Oscillatoria agardhii [23, 24]
Crystal structures for two members of the OAAH lectin family, PFA and MBHA, were determined at resolutions of 1.70 and 1.60 Å, respectively, as well as for the ␣3,␣6-mannopentaose-bound MBHA at 1.76 Å. Structural comparison between these two new members and OAA, the founding member of the OAAH lectin family, revealed a very similar overall fold, with only minor conformational differences in the loop regions, connecting strands ␤1-␤2, ␤2-␤3, ␤4-␤5, ␤5-␤6, ␤6-␤7, and ␤7-␤8, that are caused by different crystal packing in these proteins

Summary

Introduction

The Oscillatoria agardhii agglutinin homolog (OAAH) proteins constitute a novel lectin family. Significance: Our results uncovered the structural basis of protein-carbohydrate recognition in this novel lectin family and provide insights into the molecular basis of their HIV inactivation properties. Apart from data for the founding member OAA, neither three-dimensional structures, information about carbohydrate binding specificities, nor antiviral activity data have been available up to now for any other members of the OAAH family. To elucidate the structural basis for the antiviral mechanism of OAAHs, we determined the crystal structures of Pseudomonas fluorescens and Myxococcus xanthus lectins Both proteins exhibit the same fold, resembling the founding family member, OAA, with minor differences in loop conformations. Our results provide structural details of the protein-carbohydrate interaction for this novel lectin family and insights into the molecular basis of their HIV inactivation properties

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