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TitleDisulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes.
Journal, issue, pagesLife Sci Alliance, Vol. 6, Issue 9, Year 2023
Publish dateJul 4, 2023
AuthorsXixi Zhang / Zimu Li / Yanjun Zhang / Yutong Liu / Jingjing Wang / Banghui Liu / Qiuluan Chen / Qian Wang / Lutang Fu / Peiyi Wang / Xiaolin Zhong / Liang Jin / Qihong Yan / Ling Chen / Jun He / Jincun Zhao / Xiaoli Xiong /
PubMed AbstractSARS-CoV-2 spike protein (S) is structurally dynamic and has been observed by cryo-EM to adopt a variety of prefusion conformations that can be categorized as locked, closed, and open. S-trimers ...SARS-CoV-2 spike protein (S) is structurally dynamic and has been observed by cryo-EM to adopt a variety of prefusion conformations that can be categorized as locked, closed, and open. S-trimers adopting locked conformations are tightly packed featuring structural elements incompatible with RBD in the "up" position. For SARS-CoV-2 S, it has been shown that the locked conformations are transient under neutral pH. Probably because of their transience, locked conformations remain largely uncharacterized for SARS-CoV-1 S. In this study, we introduced x1, x2, and x3 disulfides into SARS-CoV-1 S. Some of these disulfides have been shown to preserve rare locked conformations when introduced to SARS-CoV-2 S. Introduction of these disulfides allowed us to image a variety of locked and other rare conformations for SARS-CoV-1 S by cryo-EM. We identified bound cofactors and structural features that are associated with SARS-CoV-1 S locked conformations. We compare newly determined structures with other available spike structures of SARS-related CoVs to identify conserved features and discuss their possible functions.
External linksLife Sci Alliance / PubMed:37402591 / PubMed Central
MethodsEM (single particle)
Resolution2.57 - 4.05 Å
Structure data

34417

8h0x

EMDB-34417, PDB-8h0x:
Structure of SARS-CoV-1 Spike Protein with Engineered x1 Disulfide (S370C and D967C), Locked-1 Conformation
Method: EM (single particle) / Resolution: 2.57 Å

34418

8h0y

EMDB-34418, PDB-8h0y:
Structure of SARS-CoV-1 Spike Protein with Engineered x1 Disulfide (S370C and D967C), Locked-112 Conformation
Method: EM (single particle) / Resolution: 2.85 Å

34419

8h0z

EMDB-34419, PDB-8h0z:
Structure of SARS-CoV-1 Spike Protein with Engineered x1 Disulfide (S370C and D967C), Locked-122 Conformation
Method: EM (single particle) / Resolution: 2.99 Å

34420

8h10

EMDB-34420, PDB-8h10:
Structure of SARS-CoV-1 Spike Protein with Engineered x1 Disulfide (S370C and D967C), Locked-2 Conformation
Method: EM (single particle) / Resolution: 2.99 Å

34421

8h11

EMDB-34421, PDB-8h11:
Structure of SARS-CoV-1 Spike Protein with Engineered x1 Disulfide (S370C and D967C), Closed Conformation
Method: EM (single particle) / Resolution: 2.72 Å

34422

8h12

EMDB-34422, PDB-8h12:
Structure of SARS-CoV-1 Spike Protein with Engineered x2 Disulfide (G400C and V969C), Locked-2 Conformation
Method: EM (single particle) / Resolution: 3.44681 Å

34423

8h13

EMDB-34423, PDB-8h13:
Structure of SARS-CoV-1 Spike Protein with Engineered x2 Disulfide (G400C and V969C), Closed Conformation
Method: EM (single particle) / Resolution: 4.05 Å

34424

8h14

EMDB-34424, PDB-8h14:
Structure of SARS-CoV-1 Spike Protein with Engineered x3 Disulfide (D414C and V969C), Locked-1 Conformation
Method: EM (single particle) / Resolution: 3.39 Å

34425

8h15

EMDB-34425, PDB-8h15:
Structure of SARS-CoV-1 Spike Protein (S/native) at pH 5.5, Closed Conformation
Method: EM (single particle) / Resolution: 3.14182 Å

34426

8h16

EMDB-34426, PDB-8h16:
Structure of SARS-CoV-1 Spike Protein (S/native) at pH 5.5, Open Conformation
Method: EM (single particle) / Resolution: 3.35534 Å

Chemicals

ChemComp-EIC:
LINOLEIC ACID / Linoleic acid

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-BLA:
BILIVERDINE IX ALPHA

Source
  • severe acute respiratory syndrome coronavirus
KeywordsVIRAL PROTEIN / PROTEIN ENGINEERING / SPIKE PROTEIN / SARS-COV-1 / SARS-COV

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