2B5Q

Solution structure of globular conformation of CMrVIA lambda conotoxin

2B5Q の概要

• エントリーDOI: 10.2210/pdb2b5q/pdb
• 関連するPDBエントリー: 1IE0 2B5P
• 分子名称: Lambda-conotoxin CMrVIA (1 entity in total)
• 機能のキーワード: conotoxin, disulfide linkage, ribbon conformation, toxin
• 細胞内の位置: Secreted: P58807
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1243.54

構造登録者

Kang, T.S.,Jois, S.D.S.,Kini, R.M. (登録日: 2005-09-29, 公開日: 2006-08-29, 最終更新日: 2022-03-09)

主引用文献

Kang, T.S.,Jois, S.D.S.,Kini, R.M.
Solution Structures of Two Structural Isoforms of CMrVIA chi/lambda-Conotoxin
Biomacromolecules, 7:2337-2346, 2006

PubMed Abstract: alpha-Conotoxins possess a conserved four-cysteine framework and disulfide linkages (C(1)(-)(3), C(2)(-)(4)) that fold toward the globular conformation with absolute fidelity. Despite the presence of a similar conserved set of cysteine framework, chi/lambda-conotoxins adopt an alternate disulfide-pairing (C(1)(-)(4), C(2)(-)(3)) and its consequent ribbon conformation, exhibiting distinct biological activities from alpha-conotoxins. chi/lambda-Conotoxin CMrVIA (VCCGYKLCHOC-COOH) isolated from the venom of Conus marmoreus natively exists in the ribbon conformation and induces seizures in mice at a potency that is of three orders higher than the non-native globular form. We have chemically synthesized two isoforms of CMrVIA conotoxin in the ribbon and globular conformation and determined their structures by (1)H NMR spectroscopy. The ribbon (PDB ID 2B5P) and globular conformations (PBD ID 2B5Q) were calculated to have paired-wise backbone RMSDs of 0.48 +/- 0.1 and 0.58 +/- 0.1 A respectively. Unlike the native globular alpha-conotoxins, the globular canonical form of CMrVIA chi/lambda-conotoxin exhibited heterogeneity in its solution structure as noted by the presence of minor conformers and poorer RMSD of structure calculation. Paired-wise backbone comparison between the native ribbon and the non-native globular form of CMrVIA conotoxin revealed an RMSD of 4.73 A, emphasizing their distinct conformational differences. These structural data are essential for the understanding of the structure-function activity of chi/lambda-conotoxins, as well as unraveling the folding propensities of these short peptide toxins.

PubMed: 16903680
DOI: 10.1021/bm060269w

実験手法

SOLUTION NMR