1DGQ

NMR SOLUTION STRUCTURE OF THE INSERTED DOMAIN OF HUMAN LEUKOCYTE FUNCTION ASSOCIATED ANTIGEN-1

1DGQ の概要

• エントリーDOI: 10.2210/pdb1dgq/pdb
• 関連するPDBエントリー: 1LFA 1ZON 1ZOO 1ZOP
• NMR情報: BMRB: 4553
• 分子名称: LEUKOCYTE FUNCTION ASSOCIATED ANTIGEN-1 (1 entity in total)
• 機能のキーワード: rossmann fold, immune system
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P20701
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21425.56

構造登録者

Legge, G.B.,Kriwacki, R.W.,Chung, J.,Hommel, U.,Ramage, P.,Case, D.A.,Dyson, H.J.,Wright, P.E. (登録日: 1999-11-24, 公開日: 2000-02-03, 最終更新日: 2024-05-22)

主引用文献

Legge, G.B.,Kriwacki, R.W.,Chung, J.,Hommel, U.,Ramage, P.,Case, D.A.,Dyson, H.J.,Wright, P.E.
NMR solution structure of the inserted domain of human leukocyte function associated antigen-1.
J.Mol.Biol., 295:1251-1264, 2000

PubMed Abstract: The interaction between the leukocyte function-associated antigen-1 (LFA-1) and the intercellular adhesion molecule is thought to be mediated primarily via the inserted domain (I-domain) in the alpha-subunit. The activation of LFA-1 is an early step in triggering the adhesion of leukocytes to target cells decorated with intercellular adhesion molecules. There is some disagreement in the literature over the respective roles of conformational changes in the I-domain and of divalent cations (Mg(2+), Mn(2+)) in the activation of LFA-1 for intercellular adhesion molecule binding. X-ray crystallographic structures of the I-domains of LFA-1 and Mac-1 in the presence and absence of cations show structural differences in the C-terminal alpha-helix; this change was proposed to represent the active and inactive conformations of the I-domain. However, more recent X-ray results have called this proposal into question. The solution structure of the Mg(2+) complex of the I-domain of LFA-1 has been determined by NMR methods, using a model-based approach to nuclear Overhauser enhancement spectroscopy peak assignment. The protein adopts the same structure in solution as that of the published I-domain X-ray structures, but the C-terminal region, where the X-ray structures are most different from each other, is different again in the solution structures. The secondary structure of this helix is well formed, but NMR relaxation data indicate that there is considerable flexibility present, probably consisting of breathing or segmental motion of the helix. The conformational diversity seen in the various X-ray structures could be explained as a result of the inherent flexibility of this C-terminal region and as a result of crystal contacts. Our NMR data are consistent with a model where the C-terminal helix has the potential flexibility to take up alternative conformations, for example, in the presence and absence of the intercellular adhesion molecule ligand. The role of divalent cations appears from our results not to be as a direct mediator of a conformational change that alters affinity for the ligand. Rather, the presence of the cation appears to be involved in some other way in ligand binding, perhaps by acting as a bridge to the ligand and by modulation of the charge of the binding surface.

PubMed: 10653701
DOI: 10.1006/jmbi.1999.3409

実験手法

SOLUTION NMR