PDBsum entry 6nip

Viral protein/immune system

PDB id

6nip

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Contents

			Protein chains

					221 a.a.


					214 a.a.


					399 a.a.

PDB id:

6nip

Links

Name:

Viral protein/immune system

Title:

Crystal structure of a human anti-zikv-denv neutralizing antibody mz1 in complex with zikv e glycoprotein

Structure:

Mz1 heavy chain. Chain: a, h. Engineered: yes. Mz1 light chain. Chain: b, l. Engineered: yes. Envelope protein e. Chain: z, e. Engineered: yes

Source:

Homo sapiens. Organism_taxid: 9606. Gene: ighv4-59 08. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: expi293. Gene: iglv1-44 01. Zika virus (isolate zikv/human/french polynesia/10087pf/2013).

Resolution:

4.16Å

R-factor:

0.190

R-free:

0.237

Authors:

R.S.Sankhala,V.Dussupt,G.Donofrio,M.Choe,K.Modjarrad,N.L.Michael, S.J.Krebs,M.G.Joyce

Key ref:

V.Dussupt et al. (2020). Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor. Nat Med, 26, 228-235. PubMed id: 32015557 DOI: 10.1038/s41591-019-0746-2

Date:

31-Dec-18

Release date:

25-Dec-19

PROCHECK

	Headers

	References

Protein chains

No UniProt id for this chain

Struc:					221 a.a.

Protein chains

No UniProt id for this chain

Struc:					214 a.a.

Protein chains

A0A024B7W1 (POLG_ZIKVF) - Genome polyprotein from Zika virus (isolate ZIKV/Human/French Polynesia/10087PF/2013)

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:					3423 a.a. 399 a.a.

Key:

PfamA domain

Secondary structure



		Enzyme reactions

Enzyme class 1:

Chains Z, E: E.C.2.1.1.56 - mRNA (guanine-N(7))-methyltransferase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

a 5'-end (5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L- methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-homocysteine

5'-end (5'-triphosphoguanosine)-ribonucleoside in mRNA	+	S-adenosyl-L- methionine	=	5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA	+	S-adenosyl-L-homocysteine

Enzyme class 2:

Chains Z, E: E.C.2.1.1.57 - methyltransferase cap1.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)- (2'-O-methyl-ribonucleoside) in mRNA + S-adenosyl-L-homocysteine + H⁺

5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA	+	S-adenosyl-L-methionine	=	5'-end (N(7)-methyl 5'-triphosphoguanosine)- (2'-O-methyl-ribonucleoside) in mRNA	+	S-adenosyl-L-homocysteine	+	H(+)

Enzyme class 3:

Chains Z, E: E.C.2.7.7.48 - RNA-directed Rna polymerase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate

RNA(n)	+	ribonucleoside 5'-triphosphate	=	RNA(n+1)	+	diphosphate

Enzyme class 4:

Chains Z, E: E.C.3.4.21.91 - flavivirin.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

Selective hydrolysis of Xaa-Xaa-|-Xbb bonds in which each of the Xaa can be either Arg or Lys and Xbb can be either Ser or Ala.

Enzyme class 5:

Chains Z, E: E.C.3.6.1.15 - nucleoside-triphosphate phosphatase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + phosphate + H⁺

ribonucleoside 5'-triphosphate	+	H2O	=	ribonucleoside 5'-diphosphate	+	phosphate	+	H(+)

Enzyme class 6:

Chains Z, E: E.C.3.6.4.13 - Rna helicase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

ATP + H2O = ADP + phosphate + H⁺

ATP	+	H2O	=	ADP	+	phosphate	+	H(+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/s41591-019-0746-2	Nat Med 26:228-235 (2020)
PubMed id: 32015557

Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor.

V.Dussupt, R.S.Sankhala, G.D.Gromowski, G.Donofrio, R.A.De La Barrera, R.A.Larocca, W.Zaky, L.Mendez-Rivera, M.Choe, E.Davidson, M.K.McCracken, J.D.Brien, P.Abbink, H.Bai, A.L.Bryan, C.H.Bias, I.M.Berry, N.Botero, T.Cook, N.A.Doria-Rose, A.G.I.Escuer, J.A.Frimpong, A.Geretz, M.Hernandez, B.S.Hollidge, N.Jian, K.Kabra, D.J.Leggat, J.Liu, A.K.Pinto, W.Rutvisuttinunt, I.Setliff, U.Tran, S.Townsley, B.J.Doranz, M.Rolland, A.B.McDermott, I.S.Georgiev, R.Thomas, M.L.Robb, K.H.Eckels, E.Barranco, M.Koren, D.R.Smith, R.G.Jarman, S.L.George, K.E.Stephenson, D.H.Barouch, K.Modjarrad, N.L.Michael, M.G.Joyce, S.J.Krebs.

ABSTRACT

Zika virus (ZIKV) has caused significant disease, with widespread cases of neurological pathology and congenital neurologic defects. Rapid vaccine development has led to a number of candidates capable of eliciting potent ZIKV-neutralizing antibodies (reviewed in refs. ^1-3). Despite advances in vaccine development, it remains unclear how ZIKV vaccination affects immune responses in humans with prior flavivirus immunity. Here we show that a single-dose immunization of ZIKV purified inactivated vaccine (ZPIV)^4-7 in a dengue virus (DENV)-experienced human elicited potent cross-neutralizing antibodies to both ZIKV and DENV. Using a unique ZIKV virion-based sorting strategy, we isolated and characterized multiple antibodies, including one termed MZ4, which targets a novel site of vulnerability centered on the Envelope (E) domain I/III linker region and protects mice from viremia and viral dissemination following ZIKV or DENV-2 challenge. These data demonstrate that Zika vaccination in a DENV-experienced individual can boost pre-existing flavivirus immunity and elicit protective responses against both ZIKV and DENV. ZPIV vaccination in Puerto Rican individuals with prior flavivirus experience yielded similar cross-neutralizing potency after a single vaccination, highlighting the potential benefit of ZIKV vaccination in flavivirus-endemic areas.