Structure of coagulation factors IX/X-binding protein, a heterodimer of C-type lectin domains

Mizuno, Hiroshi; Fujimoto, Zui; Koizumi, Masaru; Kano, Hiromi; Atoda, Hideko; Morita, Takashi

doi:10.1038/nsb0697-438

Cited by 137 publications

(151 citation statements)

References 15 publications

Supporting

Mentioning

147

Contrasting

Order By: Relevance

“…Both subunits show a similarity to carbohydrate recognition domains of the classic C-type lectins. The crystal structure of IX/X-bp (15) shows that the two subunits are tightly associated by domain swapping, and this dimerization results in the creation of the concave surface predicted to function as a coagulation factor binding site. Examination of the crystal structure of the complex between X-bp and the ␥-carboxyglutamic acid (Gla) domain of factor X has revealed that the binding site is, in fact, the concave surface (16).…”

mentioning

confidence: 99%

Crystal Structure of von Willebrand Factor A1 Domain Complexed with Snake Venom, Bitiscetin

Maita

Nishio

Nishimoto

et al. 2003

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

mentioning

confidence: 99%

Crystal Structure of von Willebrand Factor A1 Domain Complexed with Snake Venom, Bitiscetin

Maita

Nishio

Nishimoto

et al. 2003

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

“…Only a few proteins are known to swap a central element. In the blood coagulant factor IX͞X-bp, internal loops are swapped (26). In the cyclophilin Asp f 11, two neighboring strands of a central five-stranded ␤-sheet are swapped between two subunits (27).…”

Section: Structure Of Sr␤mentioning

confidence: 99%

Homodimerization of the G protein SRβ in the nucleotide-free state involves proline cis/trans isomerization in the switch II region

Schwartz

Schmidt

Brohawn

et al. 2006

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

View full text Add to dashboard Cite

Protein translocation across and insertion into membranes is essential to all life forms. Signal peptide-bearing nascent polypeptide chains emerging from the ribosome are first sampled by the signal-recognition particle (SRP), then targeted to the membrane via the SRP receptor (SR), and, finally, transferred to the proteinconducting channel. In eukaryotes, this process is tightly controlled by the concerted action of three G proteins, the 54-kD subunit of SRP and the ␣-and ␤-subunits of SR. We have determined the 2.2-Å crystal structure of the nucleotide-free SR␤ domain. Unexpectedly, the structure is a homodimer with a highly intertwined interface made up of residues from the switch regions of the G domain. The remodeling of the switch regions does not resemble any of the known G protein switch mechanisms. Biochemical analysis confirms homodimerization in vitro, which is incompatible with SR␣ binding. The switch mechanism involves cis͞trans isomerization of a strictly conserved proline, potentially implying a new layer of regulation of cotranslational transport.cotranslational transport ͉ proline isomerization ͉ signal-recognition particle receptor N ascent proteins, destined for secretion or membrane insertion, are first targeted to the endoplasmic reticulum (ER) in eukaryotes or the plasma membrane in bacteria. Targeting in eukaryotes occurs primarily via the conserved signal-recognition particle (SRP) pathway (1). This cyclic pathway starts with SRP, a ribonucleoprotein complex consisting of the 300-nucleotide SRP-RNA and six proteins, recognizing a ribosome-nascent chain (RNC) complex and arresting translation. In a second step, the stalled SRP-RNC complex docks with the ER membranebound SRP receptor (SR) (2, 3), which is dynamically associated with the protein-conducting channel (PCC or Sec61 complex) (4). Third, the RNC is detached from the SRP, binds to the PCC, and releases the nascent polypeptide chain into an aqueous pore in the channel (5, 6). Protein synthesis can then continue. Concomitantly, SRP and SR dissociate, ready for a new cycle of protein targeting. GTP binding and hydrolysis by three synchronized G proteins regulate the process and ensure unidirectionality (7,8).Intense investigation of the protein targeting process by x-ray crystallography and cryoelectron microscopy has lead to the structural characterization of domains and interactions (9, 10). As a result of these advances, several key steps are now relatively well understood. The recent cryoelectron microscopic structure of the SRP-RNC complex shows how the elongated SRP wraps around the large ribosomal subunit, binding the N-terminal signal sequence of the nascent chain at the exit tunnel via SRP54 at one end of the molecule and arresting translation by blocking the elongation-factor-binding site with its other end (11). SRP54, the only SRP protein with a bacterial homologue, has two functional domains; the C-terminal M domain is the signal sequence-binding interface, and the N-terminal composite NG domain has regulatory GTPase acti...

show abstract

“…The amino-acid sequence of each subunit shows homology with the carbohydrate-recognition domains of the classic C-type lectins, although lectin activity has not been reported. We ®rst determined the crystal structure of a CLP using IX/X-bp (Mizuno et al, 1997). The structure showed that the two subunits were intimately associated by domain swapping and that this dimerization resulted in the disruption of the lectin active site and the creation of a concave surface serving as an expected coagulation factor binding site.…”

Section: Introductionmentioning

confidence: 99%

“…The structure showed that the two subunits were intimately associated by domain swapping and that this dimerization resulted in the disruption of the lectin active site and the creation of a concave surface serving as an expected coagulation factor binding site. To date, the crystal structures of factor IX binding protein (IX-bp) from habu snake venom (Mizuno et al, 1999), the complex between IX-bp and the -carboxyglutamic acid (Gla) domain of bovine factor IX (Shikamoto et al, 2003) and the complex between factor X binding protein (X-bp) from Deinagkistrodon acutus and the Gla domain of factor X (Mizuno et al, 2001) have been determined. These CLP structures are very similar to each other and the complex structures have revealed that the binding site is in fact the concave surface.…”

Section: Introductionmentioning

confidence: 99%

“…We then prepared crystals of IX-bp from habu snake venom at pH 6.5 in the presence of a low concentration of Ca 2+ in order to investigate which subunit contained the high-af®nity Ca 2+ -binding site. Furthermore, we prepared crystals of IX-bp at pH 4.6 as the apo form in order to study the pH-dependent Ca 2+ -releasing mechanism by comparing the structures around the Ca 2+ -binding sites at different pH values including pH 7.8 (Mizuno et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Crystallization and preliminary X-ray analysis of coagulation factor IX-binding protein from habu snake venom at pH 6.5 and 4.6

et al. 2004

Self Cite

View full text Add to dashboard Cite

Coagulation factor IX-binding protein isolated from Trimeresurus¯avoviridis (IX-bp) is a C-type lectin-like protein. It is an anticoagulant protein consisting of homologous subunits A and B. The subunits both contain a Ca 2+ -binding site with differing af®nity (K d values of 14 and 130 mM at pH 7.5). These binding characteristics are pH-dependent; under acidic conditions, the af®nity of the low-af®nity site was reduced considerably. In order to identify which site has high af®nity and also to investigate the Ca 2+ -releasing mechanism, IX-bp was crystallized at pH 6.5 and 4.6. The crystals at pH 6.5 and 4.6 diffracted to 1.72 and 2.29 A Ê resolution, respectively; the former crystals belong to the monoclinic space group P2 1 , with unit-cell parameters a = 60.7, b = 63.5, c = 66.9 A Ê , = 117.0 , while the latter belong to the monoclinic space group C2, with a = 134.1, b = 37.8, c = 55.8 A Ê , = 110.4 .

show abstract

Structure of coagulation factors IX/X-binding protein, a heterodimer of C-type lectin domains

Abstract: Coagulation factors IX/X-binding protein is an intertwined dimer with a central loop projecting into the adjoining subunit. Excluding this loop, each subunit has a fold similar to rat mannose-binding protein.

Cited by 137 publications

References 15 publications

Crystal Structure of von Willebrand Factor A1 Domain Complexed with Snake Venom, Bitiscetin

Crystal Structure of von Willebrand Factor A1 Domain Complexed with Snake Venom, Bitiscetin

Homodimerization of the G protein SRβ in the nucleotide-free state involves proline cis/trans isomerization in the switch II region

Crystallization and preliminary X-ray analysis of coagulation factor IX-binding protein from habu snake venom at pH 6.5 and 4.6

Contact Info

Product

Resources

About