# High-Resolution Imaging of Human Cancer Proteins Using Microprocessor Materials.

> **Reliability concern:** This paper was retracted on 2024-11-04. See notice: 10.1002/cbic.202400798.

- **DOI:** [10.1002/cbic.202200310](https://doi.org/10.1002/cbic.202200310)
- **Rating:** Sound (3.2 out of 5)
- **Verdict:** First full-length native p53 cryo-EM structure via SiN microchips, constrained by modest resolution and absent data deposition.
- **Framework version:** v5.0
- **Pipeline version:** v0.4
- **Evaluation date:** 2026-06-01
- **Evaluation page:** https://www.nabu.science/paper/10.1002%2Fcbic.202200310

## Strengths

- **Novel substrate enables imaging of small native proteins** The SiN microchip functionalization with Ni-NTA films addresses a documented limitation in cryo-EM sample preparation for small proteins (<100 kDa), demonstrated by the failure of conventional holey carbon and patterned gold grids to retain p53 particles. This provides a reproducible, commercially available alternative.
  - Dimension: contribution
  - Location: Results, SiN Microchips for Cryo-EM Applications; Figure 1C-E
- **Biologically meaningful dimer interface maps to cancer mutations** The inactive dimer interface residues overlap with known cancer hot spot mutations (R175, R248-249, R273, R280, R282-R283, G245, G293, E294), providing a structural rationale for mutation effects that was previously unavailable for full-length native p53.
  - Dimension: contribution
  - Location: Results, Inactive P53 Assemblies Limit DNA Engagement; Figures 3B-C
- **Competent cryo-EM and modeling pipeline with validation** The image processing workflow uses standard tools (RELION, CTFFIND-4.1) with appropriate symmetry treatment (C2 for dimer), and the molecular modeling pipeline includes MolProbity validation. The use of SDS-PAGE and western blot analysis provides orthogonal confirmation of the dimer molecular weight (~100 kDa).
  - Dimension: methodological rigour
  - Location: Experimental Section; Table 1; Figure 1B

## Limitations

- **Small particle count and indirect detector limit resolution confidence** The claimed 4.2 Å resolution from ~8,000 particles on a 200 kV Talos F200C with a CETA (indirect) camera is at the optimistic boundary of what has been reported in the literature. Modern high-resolution cryo-EM structures typically use tens of thousands to millions of particles with direct electron detectors.
  - Dimension: methodological rigour
  - Location: Table 1; Experimental Section, EM Data Collection and Image Processing
- **No EMDB/PDB data deposition reported** For a 2024 structural biology paper, deposition of EM density maps and refined atomic coordinates in EMDB/PDB is a community standard expectation. The absence of any mention of deposition significantly limits independent verification of the reported structures.
  - Dimension: methodological rigour
  - Location: Experimental Section; no deposition statement present
- **Active state model is entirely computational** The DNA-bound active p53 dimer model is produced by superimposing the new full-length p53 model onto the crystal structure DBD-DNA complex (PDB 2AC0), not by experimental cryo-EM determination. This limits the strength of claims about the activation mechanism and conformational transitions described in Figure 5 and Movies S5-S7.
  - Dimension: contribution
  - Location: Results, Conformational Changes Support DNA Binding Events; Figure 4; Figure 5

## Reliability checks

Concerns (4 of 4 checks).

- **Internal coherence:** Noted. The paper is broadly self-consistent in its core structural claims, but contains a buffer composition discrepancy between sections and overclaiming in the abstract regarding 'primary brain tumors' when U87MG is an established cell line.
- **Research conduct:** Noted. No data deposition in EMDB/PDB is mentioned despite 2024 community standards for structural biology, and no conflict of interest or ethics approval statements are present.
- **Reference integrity:** Clean. All 48 cited references resolved to real publications via PubMed, Crossref, or OpenAlex.
  - References not verified automatically are resolved manually within 24 hours.

## Post-publication record

- **Status:** Concern
- **Summary:** This paper was retracted on 2024-11-04. See notice: 10.1002/cbic.202400798.
- **Last checked:** 2026-10-17