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

References listed in PDB file

Key reference

• Title: Structural basis of transcobalamin recognition by human cd320 receptor.
• Authors: A.Alam, J.S.Woo, J.Schmitz, B.Prinz, K.Root, F.Chen, J.S.Bloch, R.Zenobi, K.P.Locher.
• Ref.: Nat Commun, 2016, 7, 12100. [DOI no: 10.1038/ncomms12100]
• PubMed id: 27411955

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.