3LL1

Monomeric Griffithsin with a Single Gly-Ser Insertion and Mutations to Remove Residual Self-Association

3LL1 の概要

• エントリーDOI: 10.2210/pdb3ll1/pdb
• 関連するPDBエントリー: 2gty 2guc 2gud 2gue 2gux 2hyq 2hyr 2nu5 2nuo 3LKY 3LL0 3LL2
• 分子名称: Griffithsin, CHLORIDE ION (3 entities in total)
• 機能のキーワード: lectin, sugar-binding, anti-hiv, high mannose, man9, gp120, gp41, jacalin-related, mannose-binding, sugar binding protein
• 由来する生物種: Griffithsia (Red alga)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12663.08

構造登録者

Moulaei, T.,Wlodawer, A. (登録日: 2010-01-28, 公開日: 2010-10-06, 最終更新日: 2023-09-06)

主引用文献

Moulaei, T.,Shenoy, S.R.,Giomarelli, B.,Thomas, C.,McMahon, J.B.,Dauter, Z.,O'Keefe, B.R.,Wlodawer, A.
Monomerization of viral entry inhibitor griffithsin elucidates the relationship between multivalent binding to carbohydrates and anti-HIV activity.
Structure, 18:1104-1115, 2010

PubMed Abstract: Mutations were introduced to the domain-swapped homodimer of the antiviral lectin griffithsin (GRFT). Whereas several single and double mutants remained dimeric, insertion of either two or four amino acids at the dimerization interface resulted in a monomeric form of the protein (mGRFT). Monomeric character of the modified proteins was confirmed by sedimentation equilibrium ultracentrifugation and by their high resolution X-ray crystal structures, whereas their binding to carbohydrates was assessed by isothermal titration calorimetry. Cell-based antiviral activity assays utilizing different variants of mGRFT indicated that the monomeric form of the lectin had greatly reduced activity against HIV-1, suggesting that the antiviral activity of GRFT stems from crosslinking and aggregation of viral particles via multivalent interactions between GRFT and oligosaccharides present on HIV envelope glycoproteins. Atomic resolution crystal structure of a complex between mGRFT and nonamannoside revealed that a single mGRFT molecule binds to two different nonamannoside molecules through all three carbohydrate-binding sites present on the monomer.

PubMed: 20826337
DOI: 10.1016/j.str.2010.05.016

実験手法

X-RAY DIFFRACTION (0.97 Å)