8A6L

Human 4F2hc-LAT2 heterodimeric amino acid transporter in complex with anticalin D11vs

Summary for 8A6L

• Entry DOI: 10.2210/pdb8a6l/pdb
• EMDB information: 15210
• Descriptor: 4F2hc cell-surface antigen heavy chain, Large neutral amino acids transporter small subunit 2, Anticalin D11vs, ... (5 entities in total)
• Functional Keywords: complex, 4f2hc, lat2, anticalin, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 142396.93

Authors

Jeckelmann, J.M.,Fotiadis, D. (deposition date: 2022-06-18, release date: 2022-11-09, Last modification date: 2025-07-09)

Primary citation

Jeckelmann, J.M.,Lemmin, T.,Schlapschy, M.,Skerra, A.,Fotiadis, D.
Structure of the human heterodimeric transporter 4F2hc-LAT2 in complex with Anticalin, an alternative binding protein for applications in single-particle cryo-EM.
Sci Rep, 12:18269-18269, 2022

PubMed Abstract: Cryo-EM structure determination of relatively small and flexible membrane proteins at high resolution is challenging. Increasing the size and structural features by binding of high affinity proteins to the biomolecular target allows for better particle alignment and may result in structural models of higher resolution and quality. Anticalins are alternative binding proteins to antibodies, which are based on the lipocalin scaffold and show potential for theranostic applications. The human heterodimeric amino acid transporter 4F2hc-LAT2 is a membrane protein complex that mediates transport of certain amino acids and derivatives thereof across the plasma membrane. Here, we present and discuss the cryo-EM structure of human 4F2hc-LAT2 in complex with the anticalin D11vs at 3.2 Å resolution. Relative high local map resolution (2.8-3.0 Å) in the LAT2 substrate binding site together with molecular dynamics simulations indicated the presence of fixed water molecules potentially involved in shaping and stabilizing this region. Finally, the presented work expands the application portfolio of anticalins and widens the toolset of binding proteins to promote high-resolution structure solution by single-particle cryo-EM.

PubMed: 36310334
DOI: 10.1038/s41598-022-23270-1

Experimental method

ELECTRON MICROSCOPY (3.18 Å)