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Propeller Domain (propeller + domain)

Distribution by Scientific Domains

Chemistry	40%

Selected Abstracts

A novel Phe171Cys mutation in integrin ,IIb causes Glanzmann thrombasthenia by abrogating ,IIb,3 complex formation

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2004
N. Rosenberg
Summary.,Background: Glanzmann thrombasthenia (GT) is an autosomal recessive bleeding disorder characterized by lack of platelet aggregation induced by most agonists. The disease is caused by mutations in either ,IIb[glycoprotein (GP) IIb] or ,3 (GPIIIa) genes that lead to a lack or dysfunction of the integrin ,IIb,3 which serves as a fibrinogen receptor. Patients Mucocutaneous bleeding manifestations and platelet dysfunction consistent with GT were observed in three members of a Cypriot family: a 3-year-old proband, her father and her paternal uncle. Objective: To determine the molecular basis of GT in this family and to characterize possible biochemical and structural defects. Results: Analysis of the patients' platelets by fluorescence-activated cell sorting demonstrated trace amounts of ,3, no ,IIb and no ,IIb,3 on the membrane. Sequence analysis revealed a novel T607G transversion in exon 5 of the ,IIb gene predicting a Phe171Cys alteration that created a PstI recognition site. All three patients were homozygous for the mutation, the mother and paternal grandparents of the proband were heterozygous, whereas 110 healthy subjects lacked this transversion. Chinese hamster ovary cells cotransfected with cDNAs of mutated ,IIb and wild-type ,3 failed to express ,IIb,3 as shown by immunoprecipitation and immunohistochemistry experiments. Structural analysis of the ,IIb,3 model, which was based on the crystal structure of ,v,3, indicated that Phe171 plays an essential role in the interface between the ,-propeller domain of ,IIb and the ,A domain of ,3. Conclusions: A novel Phe171Cys mutation in the ,IIb gene of patients with GT is associated with abrogation of ,IIb,3 complex formation. [source]

X-ray diffraction structure of a cell-wall invertase from Arabidopsis thaliana

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 12 2006
Maureen Verhaest
Cell-wall invertases play crucial roles during plant development. They hydrolyse sucrose into its fructose and glucose subunits by cleavage of the ,1,,2 glycosidic bond. Here, the structure of the Arabidopsis thaliana cell-wall invertase 1 (AtcwINV1; gene accession code At3g13790) is described at a resolution of 2.15,Å. The structure comprises an N-terminal fivefold ,-propeller domain followed by a C-terminal domain formed by two ,-sheets. The active site is positioned in the fivefold ,-propeller domain, containing the nucleophile Asp23 and the acid/base catalyst Glu203 of the double-displacement enzymatic reaction. The function of the C-terminal domain remains unknown. Unlike in other GH 32 family enzyme structures known to date, in AtcwINV1 the cleft formed between both domains is blocked by Asn299-linked carbohydrates. A preliminary site-directed mutagenesis experiment (Asn299Asp) removed the glycosyl chain but did not alter the activity profile of the enzyme. [source]

Structural analysis of the complex of Keap1 with a prothymosin , peptide

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 4 2008
Balasundaram Padmanabhan
The Nrf2 transcription factor, which plays important roles in oxidative and xenobiotic stress, is negatively regulated by the cytoplasmic repressor Keap1. The ,-propeller/Kelch domain of Keap1, which is formed by the double-glycine repeat and C-terminal region domains (Keap1-DC), interacts directly with the Neh2 domain of Nrf2. The nuclear oncoprotein prothymosin , (ProT,) also interacts directly with Keap1 and may play a role in the dissociation of the Keap1,Nrf2 complex. The structure of Keap1-DC complexed with a ProT, peptide (amino acids 39,54) has been determined at 1.9,Å resolution. The Keap1-bound ProT, peptide possesses a hairpin conformation and binds to the Keap1 protein at the bottom region of the ,-propeller domain. Complex formation occurs as a consequence of their complementary electrostatic interactions. A comparison of the present structure with recently reported Keap1-DC complex structures revealed that the DLG and ETGE motifs of the Neh2 domain of Nrf2 and the ProT, peptide bind to Keap1 in a similar manner but with different binding potencies. [source]

Heme-hemopexin: A ,Chronosteric' heme-protein

IUBMB LIFE, Issue 11 2007
Paolo Ascenzi
Abstract Hemopexin (HPX) serves as scavenger and transporter of toxic plasma heme to the liver. HPX is formed by two four-bladed ,-propeller domains, resembling two thick disks that lock together at a 90° angle. The heme is bound between the two ,-propeller domains in a pocket formed by the interdomain linker peptide. Residues His213 and His266 coordinate the heme iron atom giving a stable bis-histidyl complex. The HPX-heme geometry is reminiscent of heme-proteins endowed with ligand binding and (pseudo-)enzymatic properties. HPX-heme binds reversibly CO, ,NO, and cyanide by detaching His213; however, O2 induces HPX-heme(II) oxidation. Furthermore, HPX-heme(II) facilitates ,NO/O2 and ,NO/peroxynitrite scavenging. Heme sequestering by HPX prevents heme-mediated activation of oxidants which induce the low-density lipoprotein oxidation. Here, ligand binding and (pseudo-)enzymatic properties of HPX-heme are reviewed. HPX, acting not only as a heme carrier but also displaying transient heme-based ligand binding and (pseudo-)enzymatic properties, could be considered a ,chronosteric' heme-protein. IUBMB Life, 59: 700-708, 2007 [source]

Hemopexin: The primary specific carrier of plasma heme,

BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION, Issue 5 2002
Marco Mattu
Abstract Hemopexin (HPX) is the primary specific carrier of plasma heme and participates in its clearance by transport to the liver. After delivering the heme intracellularly, HPX is released intact into the bloodstream. HPX is formed by two four-bladed ,-propeller domains, resembling two thick disks that lock together at a 90° angle; the face of the N-terminal ,-propeller domain packs against one edge of the C-terminal domain. Each propeller blade comprises a four-stranded antiparallel ,-sheet, with the first and the fourth blades tied together by disulfide bridges. The heme ligand is bound between the two four-bladed ,-propeller domains in a pocket formed by the interdomain linker peptide. Residues His-213 and His-266 coordinate the heme iron atom giving a stable bis-histidyl Fe(III) complex. Heme release results from opening of the heme binding pocket, through movement of the two ,-propeller domains and/or the interdomain linker peptide. [source]