3DBionotes-WS

3DBIONOTES-WS is a web application designed to automatically annotate biochemical and biomedical information onto structural models. Current sources of information include post-translational modifications, genomic variations associated to diseases, short linear motifs, immune epitopes sites, disordered regions and domain families.

Please cite us if you find this useful:

Jose Ramon Macias, Ruben Sanchez-Garcia, Pablo Conesa, Erney Ramirez-Aportela, Marta Martinez Gonzalez, Carlos Wert-Carvajal, Alberto M Parra-Perez, Joan Segura Mora, Sam Horrell, Andrea Thorn, Carlos O S Sorzano, Jose Maria Carazo, 3DBionotes COVID-19 edition, Bioinformatics, Volume 37, Issue 22, 15 November 2021, Pages 4258–4260.

https://doi.org/10.1093/bioinformatics/btab397

COVID-19 Structural Hub Example (EMD-21375)

Selected entries

7K7P

NSP1: Leader protein of 1a and 1ab polyproteins. NSP1 inhibits host cell translation by interacting with the 40S small ribosomal subunit. Slowing down infected host protein production, NSP1 facilitates efficient viral protein translation and evasion from host immune response, thus helping the virus to proliferate.

7MSW + EMD-23970

NSP2: Although its function is still unknown, NSP2 has been involved in several viral processes. Its highly-conserved Zn2+ binding site suggests that nsp2 binds RNA. It also seems to interact with host infected cell endosomes through cytoskeletal elements and with modulators of translation.

7TI9

Ubiquitin-like domain 1 of Nsp3.

5S73

MacroDomain I of NSP3 (Mac1): Domain that recognizes and hydrolizes the ADP-ribose label from proteins associated with the host innate immune response.

7THH

SARS-unique domain C of NSP3 (DPUP).

7NFV

PL-Pro: Domain Papain-like proteinase of NSP3. PL-Pro processes proteolytically three cleavage sites located at the N-terminus of the polyproteins 1a and 1ab. In addition, PL-Pro possesses a deubiquitinating/deISGylating activity and processes polyubiquitin chains from cellular substrates. It participates together with NSP4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. It also antagonizes innate immune induction of type I interferon by blocking phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. It prevents host cell NF-kappa-B signaling as well.

7LGO

NAB: Nucleic acid binding domain of NSP3.

7RQG

Y3 domain of Nsp3.

5R8T

NSP5: Protease that processes proteolytically the C-terminus of the polyproteins 1a and 1ab at seven and twelve sites, respectively.

7C2K + EMD-30275

NSP7: As cofactor of NSP12, NSP7 contributes to accomodate the template-product RNA, together with NSP8, in the RNA-dependent RNA polymerase (RdRp) catalytic complex.

6WXD

NSP9: Able to bind ssRNA, NSP9 forms a covalent RNA-protein intermediate. This RNA is first transferred by the NiRAN domain of NSP12 to NSP9 . Then, the NiRAN NSP12 domain transfers the RNA to GDP to start the building process of the RNA cap structure. Bound to the NSP12 NiRAN domain, NSP9 inhibits the guanylyl tranferase enzymatic activity of NSP12.

6ZPE

NSP10: Stimulating both NSP14 exoribonuclease and NSP16 methyltransferase activities, NSP10 plays an essential role in viral mRNA proofreading and cap methylation.

5ROB

NSP13: Its helicase RNA duplex-unwinding activity contributes to elongate the RNA product. Additionally, its fosfatase activity catalizes the first step of the mRNA cap synthesis.

5SMK

NSP14: Enzyme with two different catalytic activities: Exoribonuclease activity in its N-terminal end, and N7-methyltransferase activity in its C-terminal end. Its proofreading exoribonuclease lowers viral sensitivity to nucleoside analogs.

5SBF

NSP15: As uridylate-specific enzyme, NSP15 hydrolizes both ssRNA and dsRNA, probably to avoid trigger the host inmune response.

7L6T

NSP16: Methyltransferase that catalyzes the last reaction to build the viral mRNA cap, the methylation of the ribose 2'-OH.

6VSB + EMD-21375

Spike: Decorating surface glycoprotein that protrudes from the viral outer membrane. Several conformational changes allow its interaction with the host receptor ACE2 and membrane fusion, thus initiating the infection.

6XDC + EMD-22136

ORF3: As a viroporin, ORF3 forms cellular dimeric nonselective Ca2+ permeable cation channels that become active by oligomerizing into tetramers or higher-order oligomers. This channel activity in cells could be relevant to promote viral maturation through inhibition of autophagy and disruption of lysosomes.

7NTK

Protein E: Envelope small membrane protein. As a viroporin, it self-assembles in host membranes forming pentameric protein pores that can affect the integrity of the lipid bilayer or disrupt the membrane potential, thus facilitating the release of viral particles from host cells.

7VPH

ORF6: Although it is ot necessary for viral invasion and replication, ORF6 plays a relevant role in immune evasion. It directly interacts with the host complex Rae1-Nup98 preventing the nuclear export of host mRNA, antagonizing interferon signaling.

7CI3

ORF7a: Although dispensable for virus replication in cell culture, ORF7a acts as a immunomodulator factor that binds to immune cells and triggers inflammatory responses.

7F5F

ORF8: With a core fold similar to ORF7a, the structure of ORF8 reveals two novel dimer interfaces that allow forming host large-scale assemblies, potentially mediating immune suppression and evasion activities.

7CDZ

Nucleoprotein N-terminal domain: The nucleoprotein (N protein) is involved in viral assembly, replication and host immune response regulation. Its N-terminal domain (N-NTD) is responsible for RNA binding and packaging of the positive strand viral genome RNA into a helical ribonucleocapsid (RNP).

7CE0

Nucleoprotein C-terminal domain: The nucleoprotein (N protein) is involved in viral assembly, replication and host immune response regulation. Its C-terminal domain (N-CTD) is responsible for RNA binding and packaging of the positive strand viral genome RNA into a helical ribonucleocapsid (RNP).

7KDT + EMD-22829

ORF9b: The gene encoding this small protein overlaps the N gene. ORF9b protein interacts and blocks the substrate binding site of the host Tom70, import receptor of the translocase from the mitochondrial outer membrane (TOM) complex, involved in the activation of the mitochondrial antiviral signaling leading to apoptosis upon viral infection. In addition, ORF9b may modulate interferon and apoptosis signaling avoiding the interaction between Tom70 and Hsp70 and Hsp90 chaperones.

The web platform 3DBionotes-WS integrates multiple web services including many biological and biomedical annotations that can be analyzed in their structural context. Periodically updated with new annotations, this platform allows the study of macromolecular structures from public databases and those generated by users as well.

The interactive web viewer of 3DBionotes shows simultaneously atomic structure, map, sequence and feature annotations for the macromolecule of interest. This unified environment allows direct mapping of relevant biological annotations in the macromolecule conformational landscape.

For interoperability purposes, 3DBionotes-WS counts with a limited, but expanding, Application Programming Interface (API). Its purpose is to provide a convenient way to access the information we produce and collect to be processed by other third-party tools. In this regard, we are guided by FAIR principles (Findability, Accessibility, Interoperability, and Reuse).