PDBsum entry 4zrp

Transport protein

PDB id: 4zrp

Contents

Protein chains

400 a.a.

78 a.a.

Ligands

CNC ×2

GOL ×6

Metals

_CA ×6

Waters ×444

PDB id:

4zrp

Name:

Transport protein

Title:

Tc:cd320

Structure:

Transcobalamin-2. Chain: a, b. Synonym: tc-2,transcobalamin ii,tcii. Engineered: yes. Cd320 antigen. Chain: c, d. Fragment: unp residues 53-171. Synonym: 8d6 antigen,fdc-signaling molecule 8d6,fdc-sm-8d6, transcobalamin receptor,tcblr.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tcn2, tc2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf21. Gene: cd320, 8d6a, unq198/pro224.

Resolution:

2.10Å R-factor: 0.184 R-free: 0.208

Authors:

A.Alam,K.P.Locher

Key ref:

A.Alam et al. (2016). Structural basis of transcobalamin recognition by human CD320 receptor. Nat Commun, 7, 12100. PubMed id: 27411955 DOI: 10.1038/ncomms12100

Date:

12-May-15 Release date: 20-Jul-16

Protein chains

P20062  (TCO2_HUMAN) -  Transcobalamin-2 from Homo sapiens

Seq: 427 a.a.

Struc: 400 a.a.*

Protein chains

Q9NPF0  (CD320_HUMAN) -  CD320 antigen from Homo sapiens

Seq: 282 a.a.

Struc: 78 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1038/ncomms12100

Nat Commun 7:12100 (2016)

PubMed id: 27411955

Structural basis of transcobalamin recognition by human CD320 receptor.

A.Alam, J.S.Woo, J.Schmitz, B.Prinz, K.Root, F.Chen, J.S.Bloch, R.Zenobi, K.P.Locher.

ABSTRACT

Cellular uptake of vitamin B12 (cobalamin) requires capture of transcobalamin (TC) from the plasma by CD320, a ubiquitous cell surface receptor of the LDLR family. Here we present the crystal structure of human holo-TC in complex with the extracellular domain of CD320, visualizing the structural basis of the TC-CD320 interaction. The observed interaction chemistry can rationalize the high affinity of CD320 for TC and lack of haptocorrin binding. The in vitro affinity and complex stability of TC-CD320 were quantitated using a solid-phase binding assay and thermostability analysis. Stable complexes with TC were also observed for the disease-causing CD320ΔE88 mutant and for the isolated LDLR-A2 domain. We also determined the structure of the TC-CD320ΔE88 complex, which revealed only minor changes compared with the wild-type complex. Finally, we demonstrate significantly reduced in vitro affinity of TC for CD320 at low pH, recapitulating the proposed ligand release during the endocytic pathway.