Keyhole limpet hemocyanin (KLH): a biomedical review

Harris, J. Robin; Markl, Jürgen

doi:10.1016/s0968-4328(99)00036-0

Cited by 327 publications

(237 citation statements)

References 141 publications

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“…Such immunological differences may be complementary of life history variation. Specifically, one way in which slow-living birds might generate antibodies quicker than fast-living birds is to possess more lymphocytes receptive to the large number of epitopes of an antigen such as KLH (Cohn and Langman 1990;Harris and Markl 1999). This endpoint could be achieved during ontogeny via generation of a diverse B (and/or T) cell repertoire, which would promote responsiveness to a greater number of components of the antigen in adults (Ricklefs 1992;Klasing and Leshchinsky 1999).…”

Section: Inducible Defensesmentioning

confidence: 99%

Investment in immune defense is linked to pace of life in house sparrows

2006

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The evidence for a relationship between life history and immune defense is equivocal, although the basic premise is intuitively appealing: animals that live short lives and reproduce early and rapidly should not waste resources on defenses they might never use. One possible reason for a lack of strong support for this hypothesis could be the inherent complexity of the vertebrate immune system. Indeed, different components of the vertebrate immune system vary in their relative costs and benefits, and therefore only some defenses may complement variation in species' life history. To address this hypothesis, we compared multiple types of immune activity between two populations of house sparrows (Passer domesticus) with distinct life histories, one from Colon, Panama, which lay small clutches over an extended breeding season (i.e., slow-living) and the other from Princeton, New Jersey, which lay larger clutches in a smaller window of time (i.e., fast-living). We expected (a) that more costly types of immune defenses would be stronger in the slow-living sparrows and (2) that the slow-living sparrows would show a greater increase in whole-body energy expenditure after immune challenge compared to their fast-living counterparts. We found that secondary antibody response to a novel antigen was more rapid and energetic investment in immune activity was greater in slow-living sparrows. However, cellmediated immune activity was more robust in fast-living sparrows, and other measures of defense were not different between populations. These results provide partial support for a relationship between life history and immune defense in this species, but they also indicate that this relationship is not clear-cut. Further study is necessary to identify the influence of other factors, particular pathogen environment during development, on the architecture of the immune system of wild animals.

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Section: Inducible Defensesmentioning

confidence: 99%

Investment in immune defense is linked to pace of life in house sparrows

2006

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“…These cylinders either exist as decamers or aggregate further to form didecamers or multidecamers. The mollusc hemocyanin subunit has a molecular mass of 350-400 kDa and is a concatenation of seven or eight paralogous FUs of approximately 50 kDa each (FU-a to FU-h) on a single polypeptide chain (2,16,17). Each FU is typically made-up from two domains and bears one active site.…”

Section: Introductionmentioning

confidence: 99%

The refined structure of functional unit h of keyhole limpet hemocyanin (KLH1‐h) reveals disulfide bridges

et al. 2011

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Hemocyanins are multimeric oxygen‐transport proteins in the hemolymph of many arthropods and mollusks. The overall molecular architecture of arthropod and molluscan hemocyanin is very different, although they possess a similar binuclear type 3 copper center to bind oxygen in a side‐on conformation. Gastropod hemocyanin is a 35 nm cylindrical didecamer (2 × 10‐mer) based on a 400 kDa subunit. The latter is subdivided into eight paralogous “functional units” (FU‐a to FU‐h), each with an active site. FU‐a to FU‐f contribute to the cylinder wall, whereas FU‐g and FU‐h form the internal collar complex. Atomic structures of FU‐e and FU‐g, and a 9 Å cryoEM structure of the 8 MDa didecamer are available. Recently, the structure of keyhole limpet hemocyanin FU‐h (KLH1‐h) was presented as a Cα‐trace at 4 Å resolution. Unlike the other seven FU types, FU‐h contains an additional C‐terminal domain with a cupredoxin‐like fold. Because of the resolution limit of 4 Å, in some loops, the course of the protein backbone could not be established with high certainty yet. Here, we present a refined atomic structure of FU‐h (KLH1‐h) obtained from low‐resolution refinement, which unambiguously establishes the course of the polypeptide backbone and reveals the disulfide bridges as well as the orientation of bulky amino acids. © 2011 IUBMB IUBMB Life, 63(3): 183–187, 2011

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“…Therefore, it seemed a logical next step to follow the cDNA sequencing of HtH and OdH with determination of the sequences of their genes. In sequencing the cDNA corresponding to the HtH, the two distinct isoforms HtH1 and HtH2 previously described at the protein level were found (14,15); counterparts termed KLH1 and KLH2 have been studied in detail in another gastropod, the keyhole limpet Megathura crenulata (16), and shown to exhibit differential regulation. The hemocyanin isoforms HtH1 and HtH2 share only Ϸ65% sequence identity (4), and therefore their genes could be easily distinguished.…”

mentioning

confidence: 99%

Structures of two molluscan hemocyanin genes: Significance for gene evolution

Lieb

Altenhein

Markl

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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We present here the description of genes coding for molluscan hemocyanins. Two distantly related mollusks, Haliotis tuberculata and Octopus dofleini, were studied. The typical architecture of a molluscan hemocyanin subunit, which is a string of seven or eight globular functional units (FUs, designated a to h, about 50 kDa each), is reflected by the gene organization: a series of eight structurally related coding regions in Haliotis, corresponding to FU-a to FU-h, with seven highly variable linker introns of 174 to 3,198 bp length (all in phase 1). In Octopus seven coding regions (FU-a to FU-g) are found, separated by phase 1 introns varying in length from 100 bp to 910 bp. Both genes exhibit typical signal (export) sequences, and in both cases these are interrupted by an additional intron. Each gene also contains an intron between signal peptide and FU-a and in the 3 untranslated region. Of special relevance for evolutionary considerations are introns interrupting those regions that encode a discrete functional unit. We found that five of the eight FUs in Haliotis each are encoded by a single exon, whereas FU-f, FU-g, and FU-a are encoded by two, three and four exons, respectively. Similarly, in Octopus four of the FUs each correspond to an uninterrupted exon, whereas FU-b, FU-e, and FU-f each contain a single intron. Although the positioning of the introns between FUs is highly conserved in the two mollusks, the introns within FUs show no relationship either in location nor phase. It is proposed that the introns between FUs were generated as the eight-unit polypeptide evolved from a monomeric precursor, and that the internal introns have been added later. A hypothesis for evolution of the ring-like quaternary structure of molluscan hemocyanins is presented.

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Keyhole limpet hemocyanin (KLH): a biomedical review

Cited by 327 publications

References 141 publications

Investment in immune defense is linked to pace of life in house sparrows

Investment in immune defense is linked to pace of life in house sparrows

The refined structure of functional unit h of keyhole limpet hemocyanin (KLH1‐h) reveals disulfide bridges

Structures of two molluscan hemocyanin genes: Significance for gene evolution

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