Biomedical subjects

W E Royer

Publications and source records attributed to W E Royer.

25 records · Page 2Linked to original sources

PubMed1990

A cooperative hemoglobin with directly communicating hemes. The Scapharca inaequivalvis homodimer.

The unique functional properties of the homodimeric hemoglobin (HbI) extracted from the Arcid blood clam Scapharca inaequivalvis are discussed in the light of the unusual assembly of this protein. At variance with vertebrate hemoglobins, in S. inaequivalvis HbI, the heme-carrying E and F helices form the subunit interface and bring the heme groups almost into direct contact. This creates a new pathway for transferring information about the ligation state of the heme from one subunit to the other which allows cooperativity in the binding of heme ligands to be displayed by a homodimer. The tight coupling between the two subunits and the two heme groups also manifests itself in other reactions that are cooperative in S. inaequivalvis HbI, but not in human hemoglobin, namely, the cleavage of the proximal histidine-heme iron bond and the modification of specific residues located at the subunit interface.

Amino Acid Sequence↗

PubMed1990

Structural transitions upon ligand binding in a cooperative dimeric hemoglobin.

Comparison of the 2.4 angstrom resolution crystal structures of dimeric clam hemoglobin in the deoxygenated and carbon-monoxide liganded states shows how radically different the structural basis for cooperative oxygen binding is from that operative in mammalian hemoglobins. Heme groups are in direct communication across a novel subunit interface formed by the E and F helices. The conformational changes at this interface that accompany ligand binding are more dramatic at a tertiary level but more subtle at a quaternary level than those in mammalian hemoglobins. These findings suggest a cooperative mechanism that links ligation at one subunit with potentiation of affinity at the second subunit.

Amino Acid Sequence↗

PubMed1989

The 2.4-A crystal structure of Scapharca dimeric hemoglobin. Cooperativity based on directly communicating hemes at a novel subunit interface.

The crystal structure of the cooperative dimeric hemoglobin from the arcid clam, Scapharca inaequivalvis, has been determined in the carbonmonoxy state. The phase problem was solved for reflections with Bragg spacings greater than 3 A using anomalous scattering from the porphyrin iron atoms measured at a single wavelength in combination with molecular averaging. The model built into this electron density map has been refined at 2.4 A resolution by means of stereochemically restrained least squares minimization to a conventional R-value of 0.156. The root mean square deviation from ideal bond lengths and angles are 0.013 A and 1.7 degrees, respectively. In addition to the 2336 hemoglobin atoms, 214 water molecules have been incorporated into the model. This structure reveals the details of an assemblage of two identical myoglobin-like subunits that is radically different from vertebrate hemoglobins. The subunit interface is formed by direct apposition of the E and F helices, whereas these surfaces are external in vertebrate hemoglobins. The interface has both hydrophobic and hydrophilic character. Two symmetrically related hydrophobic regions are formed between subunits. Six residues are involved in each of these regions that pack tightly enough to exclude water but have only a few atoms in close van der Waals contact. A number of ordered water molecules line the interface and form bridging hydrogen bonds between subunits. Four intersubunit ionic interactions are formed, two of which involve negatively charged propionate groups of the porphyrin. In contrast to cooperative vertebrate hemoglobins, a hydrogen bond network provides a direct route for communication between the two heme groups.

Amino Acid Sequence↗

PubMed1988

Molecular symmetry of Lumbricus erythrocruorin.

X-ray diffraction data to a minimum Bragg spacing of 5.5 A have been collected from crystals of Lumbricus terrestris erthrocruorin, a 3.9 x 10(6)-dalton respiratory protein. Self-rotation function calculations from these data reveal D6 symmetry to a resolution of at least 6 A. These calculations show that erythrocruorin molecules pack in their crystals with molecular diads coincident with crystallographic diads along the a axis. Packing constraints limit the position of the molecular center to within 40 A of x = 1/4a.

Animals↗

PubMed1987

Crystals of Lumbricus erythrocruorin.

Lumbricus terrestris erythrocruorin, a 3.9 X 10(6) Mr respiratory protein, has been crystallized in four different forms. Despite the high molecular symmetry apparent from images in electron micrographs, only one crystal form expresses any molecular symmetry as crystallographic symmetry. The lattice parameters provide upper limits on the molecular dimensions of 267 A X 308 A X 172 A (1 A = 0.1 nm), which agree well with dimensions obtained from electron micrographs of negatively stained molecules. We have collected diffraction data to 5.5 A from type III crystals and have begun a structural analysis.

Animals↗

PubMed1986

Principles in the assembly of annelid erythrocruorins.

Erythrocruorins are giant extracellular respiratory proteins found freely dissolved in the blood of annelids. We present here results from our ultracentrifugation, electron microscopy, spectroscopy, and diffraction experiments on these erythrocruorins. These data are rationalized in terms of a three-dimensional model of the quaternary structure. The proposed structure is arranged in a hierarchy of symmetry. The implications of this structure for the assembly process are considered with special attention to uniqueness and self-limitation. The hypothesis is consistent with observations not used in its construction and it serves as a working hypothesis to focus further experimentation.

Animals↗

PubMedDate not supplied

Cooperative dimeric and tetrameric clam haemoglobins are novel assemblages of myoglobin folds.

Cooperative functioning of many protein systems depends on communication between different subunits of those systems. Perhaps the best understood cooperative protein system is the vertebrate haemoglobin tetramer, in which the subunits share a similar tertiary structure (the myoglobin fold) with each other and with myoglobins and haemoglobins from at least four different animal phyla and leguminous plants. Blood clams have cooperative tetrameric haemoglobin. In view of previous reports concerning the role of dimers in the vertebrate tetramer, the clam haemoglobins represent a very interesting model system. We report here the low-resolution three-dimensional crystal structures of the dimeric and tetrameric cooperative haemoglobins from the blood clam Scapharca inaequivalvis. We find that clam haemoglobins are made of myoglobin-like subunits but their assembly to form dimers and tetramers is quite different from that of vertebrate haemoglobin. The arrangement of the subunits provides a simple structural explanation for haem-haem interaction in the dimer and tetramer.

Allosteric Regulation↗