Structure and energetics of a non-proline cis-peptidyl linkage in a proline-202 .fwdarw. alanine carbonic anhydrase II variant

Tweedy, Neil; Nair, Satish K.; Paterno, Steven A.; Fierke, Carol A.; Christianson, D.W.

doi:10.1021/bi00092a003

Cited by 53 publications

(45 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, this hypothesis is consistent with the relative unimportance of mutagenesis of Pro313 to Ala313 [13], in that a type II B turn with Gly312 in the i + 1 and Ala313 in the i + 2 position would also be expected to be a competent thrombin-like proteolytic substrate. Alternatively, the type VI turn could be maintained in the P313A variant, as recently observed for a carbonic anhydrase II variant [36]. We suggest that this shift is essential for V, loop cleavage by thrombin, factor Xa, or related proteases.…”

Section: Discussionsupporting

confidence: 71%

Conformational rearrangements required of the V₃ loop of HIV‐1 gp120 for proteolytic cleavage and infection

et al. 1994

View full text Add to dashboard Cite

HIV gp120 is specifically cleaved at a single site in the V, loop between Arg315 and Ala316 by thrombin. Previous observations by others have indicated that binding to CD4 enhances the rate of Vg loop cleavage, and that this cleavage is a prerequisite for HIV infection. Other observations also suggest that the cleavage site is in a type II B-turn centered at Pro313 -Gly314. However, our docking experiments indicate that this conformation cannot dock to thrombin and other trypsin-like serine proteases. Thus, based on the thrombin-bound conformation of peptide substrates, we propose that CD4 binding, at a site remote from the V, loop, induces and stabilizes a trans to cis isomerization of the highly conserved residue Pro"', and that this conformational shift is a prerequisite for cleavage by a 'thrombin-like' cellular protease and subsequent infection.

show abstract

Section: Discussionsupporting

confidence: 71%

Conformational rearrangements required of the V₃ loop of HIV‐1 gp120 for proteolytic cleavage and infection

et al. 1994

View full text Add to dashboard Cite

show abstract

“…Presumably, the total dimerization interface area is large enough to tolerate the single amino acid changes, and the cis-peptide bond configuration in P89A was retained. This retention is not completely unexpected and has been observed in several other cases (30,31). To verify SR␤-specific homodimerization, we performed the gel-filtration assay with SR␤ from three additional organisms: Drosophila melanogaster, Caenorhabditis elegans, and Homo sapiens.…”

Section: Sr␤ Homodimerization In Vitrosupporting

confidence: 59%

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

“…Sci. USA 94 (1997)demonstrated unequivocally by the solution of its crystal structure (47), which showed that the cis peptide bond is retained in the mutant. During the folding of these proteins, it is likely that the local formation of ''native-like'' structure in the vicinity of the cis peptide bond provides stabilizing interactions (such as hydrogen bonds, metal ligand binding, etc.)…”

Section: Resultsmentioning

confidence: 99%

The primary fibrin polymerization pocket: Three-dimensional structure of a 30-kDa C-terminal γ chain fragment complexed with the peptide Gly-Pro-Arg-Pro

Pratt

Côté

Chung

et al. 1997

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

157

133

View full text Add to dashboard Cite

After vascular injury, a cascade of serine protease activations leads to the conversion of the soluble fibrinogen molecule into fibrin. The fibrin monomers then polymerize spontaneously and noncovalently to form a fibrin gel. The primary interaction of this polymerization reaction is between the newly exposed N-terminal Gly-Pro-Arg sequence of the ␣ chain of one fibrin molecule and the C-terminal region of a ␥ chain of an adjacent fibrin(ogen) molecule. In this report, the polymerization pocket has been identified by determining the crystal structure of a 30-kDa C-terminal fragment of the fibrin(ogen) ␥ chain complexed with the peptide Gly-Pro-Arg-Pro. This peptide mimics the N terminus of the ␣ chain of fibrin. The conformational change in the protein upon binding the peptide is subtle, with electrostatic interactions primarily mediating the association. This is consistent with biophysical experiments carried out over the last 50 years on this fundamental polymerization reaction.

show abstract

Structure and energetics of a non-proline cis-peptidyl linkage in a proline-202 .fwdarw. alanine carbonic anhydrase II variant

Cited by 53 publications

References 67 publications

Conformational rearrangements required of the V₃ loop of HIV‐1 gp120 for proteolytic cleavage and infection

Conformational rearrangements required of the V₃ loop of HIV‐1 gp120 for proteolytic cleavage and infection

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

The primary fibrin polymerization pocket: Three-dimensional structure of a 30-kDa C-terminal γ chain fragment complexed with the peptide Gly-Pro-Arg-Pro

Contact Info

Product

Resources

About

Structure and energetics of a non-proline cis-peptidyl linkage in a proline-202 .fwdarw. alanine carbonic anhydrase II variant

Cited by 53 publications

References 67 publications

Conformational rearrangements required of the V3 loop of HIV‐1 gp120 for proteolytic cleavage and infection

Conformational rearrangements required of the V3 loop of HIV‐1 gp120 for proteolytic cleavage and infection

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

The primary fibrin polymerization pocket: Three-dimensional structure of a 30-kDa C-terminal γ chain fragment complexed with the peptide Gly-Pro-Arg-Pro

Contact Info

Product

Resources

About

Conformational rearrangements required of the V₃ loop of HIV‐1 gp120 for proteolytic cleavage and infection

Conformational rearrangements required of the V₃ loop of HIV‐1 gp120 for proteolytic cleavage and infection