scholarly journals A Rare Deletion in SARS-CoV-2 ORF6 Dramatically Alters the Predicted Three-Dimensional Structure of the Resultant Protein

2020 ◽  
Author(s):  
Marco A. Riojas ◽  
Andrew M. Frank ◽  
Nikhita P. Puthuveetil ◽  
Beth Flores ◽  
Michael Parker ◽  
...  
Keyword(s):  
Selective Pressure ◽  
Type I Interferon ◽  
Clinical Sample ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Type I ◽  
Three Dimensional Structure ◽  
Clinical Patient ◽  
N Terminus ◽  
Functional Implications

AbstractThe function of the SARS-CoV-2 accessory protein p6, encoded by ORF6, is not fully known. Based upon its similarity to p6 from SARS-CoV, it may play a similar role, namely as an antagonist of type I interferon (IFN) signaling. Here we report the sequencing of a SARS-CoV-2 strain passaged six times after original isolation from a clinical patient in Hong Kong. The genome sequence shows a 27 nt in-frame deletion (Δ27,264-27,290) within ORF6, predicted to result in a 9 aa deletion (ΔFKVSIWNLD) from the central portion of p6. This deletion is predicted to result in a dramatic alteration in the three-dimensional structure of the resultant protein (p6Δ22-30), possibly with significant functional implications. Analysis of the original clinical sample indicates that the deletion was not present, while sequencing of subsequent passages of the strain identifies the deletion as a majority variant. This suggests that the deletion originated ab initio during passaging and subsequently propagated into the majority, possibly due to the removal of selective pressure through the IFN-deficient Vero E6 cell line. The specific function of the SARS-CoV-2 p6 N-terminus, if any, has not yet been determined. However, this deletion is predicted to cause a shift from N-endo to N-ecto in the transmembrane localization of the SARS-CoV-2 p6Δ22-30 N-terminus, possibly leading to the ablation of its native function.

The three-dimensional structure of an eukaryotic glutamine synthetase: Functional implications of its oligomeric structure

2006 ◽  
Vol 156 (3) ◽  
pp. 469-479 ◽  
Author(s):  
Oscar Llorca ◽  
Marco Betti ◽  
José M. González ◽  
Alfonso Valencia ◽  
Antonio J. Márquez ◽  
...  
Keyword(s):  
Glutamine Synthetase ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Oligomeric Structure ◽  
Three Dimensional Structure ◽  
Functional Implications

Zona Pellucida Proteins, Fibrils, and Matrix

2020 ◽  
Vol 89 (1) ◽  
pp. 695-715
Author(s):  
Eveline S. Litscher ◽  
Paul M. Wassarman
Keyword(s):  
Extracellular Matrix ◽  
Zona Pellucida ◽  
Three Dimensional ◽  
Structural Features ◽  
Biological Properties ◽  
Preimplantation Development ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Early Embryos ◽  
N Terminus

The zona pellucida (ZP) is an extracellular matrix that surrounds all mammalian oocytes, eggs, and early embryos and plays vital roles during oogenesis, fertilization, and preimplantation development. The ZP is composed of three or four glycosylated proteins, ZP1–4, that are synthesized, processed, secreted, and assembled into long, cross-linked fibrils by growing oocytes. ZP proteins have an immunoglobulin-like three-dimensional structure and a ZP domain that consists of two subdomains, ZP-N and ZP-C, with ZP-N of ZP2 and ZP3 required for fibril assembly. A ZP2–ZP3 dimer is located periodically along ZP fibrils that are cross-linked by ZP1, a protein with a proline-rich N terminus. Fibrils in the inner and outer regions of the ZP are oriented perpendicular and parallel to the oolemma, respectively, giving the ZP a multilayered appearance. Upon fertilization of eggs, modification of ZP2 and ZP3 results in changes in the ZP's physical and biological properties that have important consequences. Certain structural features of ZP proteins suggest that they may be amyloid-like proteins.

scholarly journals Altered affinity of insulin-like growth factor II (IGF-II) for receptors and IGF-binding proteins, resulting from limited modifications of the IGF-II molecule

1991 ◽  
Vol 278 (1) ◽  
pp. 249-254 ◽  
Author(s):  
Y Oh ◽  
M W Beukers ◽  
H M Pham ◽  
P A Smanik ◽  
M C Smith ◽  
...  
Keyword(s):  
Amino Acids ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Type I ◽  
Type Ii ◽  
Factor Ii ◽  
N Terminus ◽  
Severe Impairment ◽  
Igf Binding ◽  
Terminal Amino

The binding affinities of seven analogues of recombinant human insulin-like growth factor II (hIGF-II) were characterized for the IGF type-I and type-II receptors and insulin receptors, as well as for IGF-binding protein (IGFBP)-1, IGFBP-2, IGFPB-3 and human serum IGFBPs. A switch of two of the three cysteine bridges in hIGF-II, 9-47 and 46-51 to 9-46 and 47-51, severely impaired the binding of this analogue to all receptors and to the IGFBPs. The affinities for the IGF type-I receptor and the IGFBPs were decreased over 100-fold, while the binding to the insulin receptor and the IGF type-II receptor was less affected, with a 6-10-fold decrease in affinity. Slight modifications of the N-terminus had only minor effects upon the binding of hIGF-II to the IGFBPs or to the receptors. Deletion of both the N-terminal amino acid and the two C-terminal amino acids resulted in moderate decreases in affinity, with a 60% decrease in affinity for IGFBP-1 and the IGF type-I receptor. Acetylation of the N-terminus of Ala1 and the epsilon-nitrogen of Lys65 decreased the affinity, by 60-90%, of hIGF-II for all of the IGFBPs and receptors. The experiments involving acetylation of IGF-II or switching of its cysteine bridges indicated that these modifications (no substitution, deletion or addition of any of the 67 amino acids of hIGF-II) may lead to a severe impairment of the binding affinity of IGF-II for both the IGFBPs and the receptors. Acetylation of the epsilon-nitrogen of Lys65, which causes a charge change, or alteration of the three-dimensional structure, as shown by the cysteine bridge switch, lead to a severe impairment of the binding affinity for the binding proteins and for the receptors. In general, care should be taken with the synthesis of analogues and the interpretation of resulting binding data, since affinity alterations ascribed to amino acid changes may instead be caused by alterations of the charge or the three-dimensional structure of the protein.

scholarly journals Isocitrate dehydrogenase from bovine heart: primary structure of subunit 3/4

1995 ◽  
Vol 310 (2) ◽  
pp. 507-516 ◽  
Author(s):  
Y Zeng ◽  
C Weiss ◽  
T T Yao ◽  
J Huang ◽  
L Siconolfi-Baez ◽  
...  
Keyword(s):  
Amino Acid ◽  
Isocitrate Dehydrogenase ◽  
Three Dimensional ◽  
Alpha Subunit ◽  
Dimensional Structure ◽  
Sequence Information ◽  
Three Dimensional Structure ◽  
Catalytic Function ◽  
N Terminus ◽  
Enzyme Subunits

Bovine NAD(+)-dependent isocitrate dehydrogenase was shown previously to contain four subunits of approx. 40 kDa (subunits 1-4) possessing different peptide maps and electrophoretic properties [Rushbrook and Harvey (1978) Biochemistry 17, 5339-5346]. In this study the heterogeneity is confirmed using enzyme purified by updated methods and from single animals, ruling out allelic variability. Subunits 1 and 2 were differentiated from each other and from subunits 3 and 4 by N-terminal amino acid sequencing. Subunits 3 and 4 (subunits 3/4) were identical in sequence over 30 residues. The N-terminal residues of subunits 1 and 2 were homologous but not identical with the beta- and gamma-subunits respectively of the comparable pig heart enzyme. Subunits 3/4 were identical over 30 residues with the N-terminus of the pig heart alpha-subunit. Full-length sequence, including that for mitochondrial import, is presented for a protein with the processed N-terminus of subunits 3/4, deduced from cloned cDNA obtained utilizing the N-terminal sequence information. The derived amino acid sequence for the mature protein contains 339 amino acids and has a molecular mass of 36,685 Da. Complete identity with N-terminal and Cys-containing peptides totalling 92 residues from the alpha-subunit of the pig heart enzyme [Huang and Colman (1990) Biochemistry 29, 8266-8273] suggests that maintenance of a particular three-dimensional structure in this subunit is crucial to the function of the enzyme. An electrophoretic heterogeneity within the pig heart alpha-subunit, similar to that shown by bovine subunits 3/4, was demonstrated. One reordering of the Cys-containing peptides of the pig heart alpha-subunit is indicated. Sequence comparison with the distantly related NADP(+)-dependent enzyme from Escherichia coli, for which the three-dimensional structure is known [Stoddard, Dean and Koshland (1993) Biochemistry 32, 9310-9316] shows strong conservation of residues binding isocitrate, Mg2+ and the NAD+ moiety of NADP+, consistent with a catalytic function.

The three-dimensional structure of canine parvovirus and its functional implications

Science ◽  
1991 ◽  
Vol 251 (5000) ◽  
pp. 1456-1464 ◽  
Author(s):  
J Tsao ◽  
M. Chapman ◽  
M Agbandje ◽  
W Keller ◽  
K Smith ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Canine Parvovirus ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Functional Implications

Functional implications of interleukin-1β based on the three-dimensional structure

1992 ◽  
Vol 12 (1) ◽  
pp. 10-23 ◽  
Author(s):  
B. Veerapandian ◽  
Gary L. Gilliland ◽  
Reetta Raag ◽  
Anders L. Svensson ◽  
Yoshihiro Masui ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Interleukin 1Β ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Functional Implications

The Three-Dimensional Structure of Canine Parvovirus and Its Functional Implications

2014 ◽  
pp. 230-238
Author(s):  
Jun Tsao ◽  
Michael S. Chapman ◽  
Mavis Agbandje ◽  
Walter Keller ◽  
Kathy Smith ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Canine Parvovirus ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Functional Implications
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