2BB5

Structure of Human Transcobalamin in complex with Cobalamin

2BB5 の概要

• エントリーDOI: 10.2210/pdb2bb5/pdb
• 関連するPDBエントリー: 2BB6 2BBC
• 分子名称: Transcobalamin II, COBALAMIN (3 entities in total)
• 機能のキーワード: alpha_6 - alpha_6 barrel, transport protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P20062
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 93899.54

構造登録者

Wuerges, J.,Garau, G.,Geremia, S.,Fedosov, S.N.,Petersen, T.E.,Randaccio, L. (登録日: 2005-10-17, 公開日: 2006-04-04, 最終更新日: 2024-10-30)

主引用文献

Wuerges, J.,Garau, G.,Geremia, S.,Fedosov, S.N.,Petersen, T.E.,Randaccio, L.
Structural basis for mammalian vitamin B12 transport by transcobalamin.
Proc.Natl.Acad.Sci.Usa, 103:4386-4391, 2006

PubMed Abstract: Cobalamin (Cbl, vitamin B(12)) serves for two essential cofactors in mammals. The pathway for its intestinal absorption, plasma transport, and cellular uptake uses cell surface receptors and three Cbl-transporting proteins, haptocorrin, intrinsic factor, and transcobalamin (TC). We present the structure determination of a member of the mammalian Cbl-transporter family. The crystal structures of recombinant human and bovine holo-TCs reveal a two-domain architecture, with an N-terminal alpha(6)-alpha(6) barrel and a smaller C-terminal domain. One Cbl molecule in base-on conformation is buried inside the domain interface. Structural data combined with previous binding assays indicate a domain motion in the first step of Cbl binding. In a second step, the weakly coordinated ligand H(2)O at the upper axial side of added H(2)O-Cbl is displaced by a histidine residue of the alpha(6)-alpha(6) barrel. Analysis of amino acid conservation on TC's surface in orthologous proteins suggests the location of the TC-receptor-recognition site in an extended region on the alpha(6)-alpha(6) barrel. The TC structure allows for the mapping of sites of amino acid variation due to polymorphisms of the human TC gene. Structural information is used to predict the overall fold of haptocorrin and intrinsic factor and permits a rational approach to the design of new Cbl-based bioconjugates for diagnostic or therapeutic drug delivery.

PubMed: 16537422
DOI: 10.1073/pnas.0509099103

実験手法

X-RAY DIFFRACTION (3.2 Å)