5UM8

Crystal structure of HIV-1 envelope trimer 16055 NFL TD CC (T569G) in complex with Fabs 35022 and PGT124

Summary for 5UM8

• Entry DOI: 10.2210/pdb5um8/pdb
• Descriptor: glycoprotein gp120, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (13 entities in total)
• Functional Keywords: hiv-1 antibody glycoprotein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 6
• Total formula weight: 179603.35

Authors

Garces, F.,Stanfield, R.L.,Wilson, I.A. (deposition date: 2017-01-26, release date: 2017-05-24, Last modification date: 2024-10-30)

Primary citation

Guenaga, J.,Garces, F.,de Val, N.,Stanfield, R.L.,Dubrovskaya, V.,Higgins, B.,Carrette, B.,Ward, A.B.,Wilson, I.A.,Wyatt, R.T.
Glycine Substitution at Helix-to-Coil Transitions Facilitates the Structural Determination of a Stabilized Subtype C HIV Envelope Glycoprotein.
Immunity, 46:792-803.e3, 2017

PubMed Abstract: Advances in HIV-1 envelope glycoprotein (Env) design generate native-like trimers and high-resolution clade A, B, and G structures and elicit neutralizing antibodies. However, a high-resolution clade C structure is critical, as this subtype accounts for the majority of HIV infections worldwide, but well-ordered clade C Env trimers are more challenging to produce due to their instability. Based on targeted glycine substitutions in the Env fusion machinery, we defined a general approach that disfavors helical transitions leading to post-fusion conformations, thereby favoring the pre-fusion state. We generated a stabilized, soluble clade C Env (16055 NFL) and determined its crystal structure at 3.9 Å. Its overall conformation is similar to SOSIP.664 and native Env trimers but includes a covalent linker between gp120 and gp41, an engineered 201-433 disulfide bond, and density corresponding to 22 N-glycans. Env-structure-guided design strategies resulted in multiple homogeneous cross-clade immunogens with the potential to advance HIV vaccine development.

PubMed: 28514686
DOI: 10.1016/j.immuni.2017.04.014

Experimental method

X-RAY DIFFRACTION (3.935 Å)