Crystal Structure of the 3.8-MDa Respiratory Supermolecule Hemocyanin at 3.0 Å Resolution

Gai, Zuoqi; Matsuno, Asuka; Kato, Kuniki; Kato, Sanae; Khan, Rafiqul Islam; Shimizu, Takeshi; Yoshioka, Toshikazu; Kato, Yuki; Kishimura, Hideki; Kanno, Gaku; Miyabe, Yoshikatsu; Terada, Tohru; Tanaka, Yoshikazu; Yao, Min

doi:10.1016/j.str.2015.09.008

Cited by 30 publications

(40 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Haemocyanins, apart from their ability to carry oxygen necessary for survival, generate reactive oxygen species in response to microbial pathogens (Iwanaga, ). The PMGs carried by mollusc haemocyanins were described to impact protomer–dimer assembly as documented using X‐ray crystallography (Gai et al ., ). Analogous to functions served by plant PMPs (Lannoo & Van Damme, ), the xylosylated PMGs may also play mediating roles in the mollusc immune response through yet‐to‐be‐reported glycan‐lectin interactions.…”

Section: Surveying Pmps Across the Eukaryotic Kingdoms And Phylamentioning

confidence: 97%

Human protein paucimannosylation: cues from the eukaryotic kingdoms

et al. 2019

View full text Add to dashboard Cite

Paucimannosidic proteins (PMPs) are bioactive glycoproteins carrying truncated α-or β-mannosyl-terminating asparagine (N )-linked glycans widely reported across the eukaryotic domain. Our understanding of human PMPs remains limited, despite findings documenting their existence and association with human disease glycobiology. This review comprehensively surveys the structures, biosynthetic routes and functions of PMPs across the eukaryotic kingdoms with the aim of synthesising an improved understanding on the role of protein paucimannosylation in human health and diseases. Convincing biochemical, glycoanalytical and biological data detail a vast structural heterogeneity and fascinating tissue-and subcellular-specific expression of PMPs within invertebrates and plants, often comprising multi-α1,3/6-fucosylation and β1,2-xylosylation amongst other glycan modifications and non-glycan substitutions e.g. O-methylation. Vertebrates and protists express less-heterogeneous PMPs typically only comprising variable core fucosylation of bi-and trimannosylchitobiose core glycans. In particular, the Manα1,6Manβ1,4GlcNAc(α1,6Fuc)β1,4GlcNAcβAsn glycan (M2F) decorates various human neutrophil proteins reportedly displaying bioactivity and structural integrity demonstrating that they are not degradation products. Less-truncated paucimannosidic glycans (e.g. M3F) are characteristic glycosylation features of proteins expressed by human cancer and stem cells. Concertedly, these observations suggest the involvement of human PMPs in processes related to innate immunity, tumorigenesis and cellular differentiation. The absence of human PMPs in diverse bodily fluids studied under many (patho)physiological conditions suggests extravascular residence and points to localised functions of PMPs in peripheral tissues. Absence of PMPs in Fungi indicates that paucimannosylation is common, but not universally conserved, in eukaryotes. Relative to human PMPs, the expression of PMPs in plants, invertebrates and protists is more tissue-wide and constitutive yet, similar to their human counterparts, PMP expression remains regulated by the physiology of the producing organism and PMPs evidently serve essential functions in development, cell-cell communication and host-pathogen/symbiont interactions. In most PMP-producing organisms, including humans, the N -acetyl-β-hexosaminidase isoenzymes and linkage-specific α-mannosidases are glycoside hydrolases critical for generating PMPs via N -acetylglucosaminyltransferase I (GnT-I)-dependent and GnT-I-independent truncation pathways. However, the identity and structure of many species-specific PMPs in eukaryotes, their biosynthetic routes, strong tissue-and development-specific expression, and diverse functions are still elusive. Deep exploration of these PMP features involving, for example, the characterisation of endogenous PMP-recognising lectins across a variety of healthy and N -acetyl-β-hexosaminidase-deficient human tissue types and identification of microbial adhesins reactive to human PMPs, are amongs...

show abstract

Section: Surveying Pmps Across the Eukaryotic Kingdoms And Phylamentioning

confidence: 97%

Human protein paucimannosylation: cues from the eukaryotic kingdoms

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In addition, FUh homology model showed an extra C-terminal cupredoxin-like motif (Fig 2C). The eight FUs presented the six-conserved Hys residues in the copper-binding site, an oxygen-binding site motif (PYWDW/T) [35], four highly conserved Cys residues forming disulfide bridges [15] and, in the case of FUh, an extra pair of Cys residues in the cupredoxin like domain [36] (Fig 2A). Seven potential N-glycosylation sites (NXS/T) were predicted all along PcH-IIa and PcH-IIb subunits while ten and eleven were predicted for PcH-III and PcH-I subunits, respectively (S1 Fig).…”

Section: Primary Structure and Bioinformatic Analysismentioning

confidence: 99%

“…Despite the biological and biomedical relevant aspects of these proteins and the fact that high-resolution structure of entire molecules were solved [15][16][17], gene structure studies of molluscan Hc are very scarce. Available gene structures show a general organization as a concatenation of exons coding the different Hc FUs, connected to each other by strictly conserved linker introns.…”

Section: Introductionmentioning

confidence: 99%

Hemocyanin of the caenogastropod Pomacea canaliculata exhibits evolutionary differences among gastropod clades

et al. 2020

View full text Add to dashboard Cite

Structural knowledge of gastropod hemocyanins is scarce. To better understand their evolution and diversity we studied the hemocyanin of a caenogastropod, Pomacea canaliculata (PcH). Through a proteomic and genomic approach, we identified 4 PcH subunit isoforms, in contrast with other gastropods that usually have 2 or 3. Each isoform has the typical Keyhole limpet-type hemocyanin architecture, comprising a string of eight globular functional units (FUs). Correspondingly, genes are organized in eight FUs coding regions. All FUs in the 4 genes are encoded by more than one exon, a feature not found in non-caenogastropods. Transmission electron microscopy images of PcH showed a cylindrical structure organized in di, tri and tetra-decamers with an internal collar structure, being the di and tridecameric cylinders the most abundant ones. PcH is N-glycosylated with high mannose and hybrid-type structures, and complex-type N-linked glycans, with absence of sialic acid. Terminal β-N-GlcNAc residues and nonreducing terminal α-GalNAc are also present. The molecule lacks O-linked glycosylation but presents the T-antigen (Gal-β1,3-GalNAc). Using an anti-PcH polyclonal antibody, no cross-immunoreactivity was observed against other gastropod hemocyanins, highlighting the presence of clade-specific structural differences among gastropod hemocyanins. This is, to the best of our knowledge, the first gene structure study of a Caenogastropoda hemocyanin.

show abstract

“…Mollusc Hcs are extremely large protein complexes dissolved in the hemolymph of gastropods and cephalopods [33, 34]. Typically, subunit molecular masses range from 330 to 450 kDa depending on the species.…”

Section: The Oxygen-transport Proteinsmentioning

confidence: 99%

Immunological properties of oxygen-transport proteins: hemoglobin, hemocyanin and hemerythrin

Coates

Decker

2016

Cell. Mol. Life Sci.

123

View full text Add to dashboard Cite

It is now well documented that peptides with enhanced or alternative functionality (termed cryptides) can be liberated from larger, and sometimes inactive, proteins. A primary example of this phenomenon is the oxygen-transport protein hemoglobin. Aside from respiration, hemoglobin and hemoglobin-derived peptides have been associated with immune modulation, hematopoiesis, signal transduction and microbicidal activities in metazoans. Likewise, the functional equivalents to hemoglobin in invertebrates, namely hemocyanin and hemerythrin, act as potent immune effectors under certain physiological conditions. The purpose of this review is to evaluate the true extent of oxygen-transport protein dynamics in innate immunity, and to impress upon the reader the multi-functionality of these ancient proteins on the basis of their structures. In this context, erythrocyte–pathogen antibiosis and the immune competences of various erythroid cells are compared across diverse taxa.Electronic supplementary materialThe online version of this article (doi:10.1007/s00018-016-2326-7) contains supplementary material, which is available to authorized users.

show abstract

Crystal Structure of the 3.8-MDa Respiratory Supermolecule Hemocyanin at 3.0 Å Resolution

Cited by 30 publications

References 41 publications

Human protein paucimannosylation: cues from the eukaryotic kingdoms

Human protein paucimannosylation: cues from the eukaryotic kingdoms

Hemocyanin of the caenogastropod Pomacea canaliculata exhibits evolutionary differences among gastropod clades

Immunological properties of oxygen-transport proteins: hemoglobin, hemocyanin and hemerythrin

Contact Info

Product

Resources

About