Evidence map›Paper›PMID 41339521›Full record

ArticleCommunications biology2025

Structure guided analysis of KRAS G12 mutants in HLA-A*11:01 reveals a length encoded immunogenic advantage in G12D.

Jiali Zhu, Zhifeng Chen, Xi Xu, Yuxuan Wang, Pei Liu, Maorong Wen, Quanmeng Wang, Yuchen He, Hongwei Jin, Hongjuan Xue and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Jiali Zhu *Department of Anesthesiology, Putuo People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Zhifeng Chen *Department of Anesthesiology, Putuo People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Xi XuDepartment of Anesthesiology, Putuo People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Yuxuan WangDepartment of Anesthesiology, Putuo People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Pei LiuDepartment of Anesthesiology, Putuo People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Maorong WenHangzhou Weizhi Biotechnology Co., Ltd, Hangzhou, China.
Quanmeng WangTongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Yuchen HeShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Hongwei JinState key laboratory of natural and biomimetic drugs, Peking University Health Science Center, Beijing, China.
Hongjuan XueNational Facility for Protein Science in Shanghai, ZhangJiang lab, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, China.
Shuqing WangTianjin Key Laboratory of Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, China.
Ke XuShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. kx2129@tongji.edu.cn.ORCID http://orcid.org/0000-0001-7552-5002
Linlin ZhaoDepartment of Anesthesiology, Putuo People's Hospital, School of Medicine, Tongji University, Shanghai, China. lzhao@tongji.edu.cn.ORCID http://orcid.org/0000-0002-2228-6877

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32571394National Natural Science Foundation of China (National Science Foundation of China) 32571410
6 · The paper itself

Abstract

KRAS G12 mutations are frequent oncogenic drivers, yet their differential immunogenicity complicates T cell-based therapies. Here, we integrate structural, biophysical, and functional analyses to examine how KRAS G12 variants remodel peptide-MHC-I (pMHC) architecture and T cell receptor (TCR) recognition. Using HLA-A*11:01, we show that single residue substitutions at position 12 induce distinct conformational changes in the MHC groove, with G12D uniquely destabilizing the complex through a buried aspartate side chain. Notably, G12D peptides adopt two registers, a 9-mer and a 10-mer, that diverge sharply in structure and immunogenicity. The 10-mer forms a compact, stable pMHC with a TCR-accessible surface, while the 9-mer adopts a bent conformation incompatible with recognition. Molecular dynamics and NMR titration confirm the superior stability and binding affinity of the 10-mer. These results highlight how peptide length and conformation critically shape immune visibility, offering mechanistic insight for optimizing TCR-T therapies against elusive neoantigens like KRAS G12D.

Indexed as

HLA-A AntigensMutationProto-Oncogene Proteins p21(ras)HumansMolecular Dynamics SimulationPeptidesProtein ConformationReceptors, Antigen, T-CellHLA-A AntigensKRAS protein, humanPeptidesProto-Oncogene Proteins p21(ras)Receptors, Antigen, T-Cell

Identifiers

PMID41339521
PMCPMC12774912

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.