Evidence map›Paper›PMID 39713448›Full record

ArticlebioRxiv : the preprint server for biology2024

Regulatory interactions between APOBEC3B N- and C-terminal domains.

Mac Kevin E Braza, Özlem Demir, Surl-Hee Ahn, Clare K Morris, Carla Calvó-Tusell, Kelly L McGuire, Bárbara de la Peña Avalos, Michael A Carpenter, Yanjun Chen, Lorenzo Casalino and 4 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. 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

5 · Who and what money

Authors and funding

14 authors.

Mac Kevin E BrazaDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA.ORCID 0000-0002-6929-7397
Özlem DemirDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA.ORCID 0000-0002-3317-4731
Surl-Hee AhnDepartment of Chemical Engineering, University of California, Davis, Davis, CA.ORCID 0000-0002-3422-805X
Clare K MorrisDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA.ORCID 0000-0002-4314-5387
Carla Calvó-TusellDepartment of Molecular Biology, University of California, San Diego, La Jolla, CA.ORCID 0000-0003-2681-8460
Kelly L McGuireDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA.ORCID 0009-0005-7520-3675
Bárbara de la Peña AvalosDepartment of Biochemistry and Structural Biology, University of Texas Health San Antonio, San Antonio, TX.ORCID 0000-0001-9796-8015
Michael A CarpenterDepartment of Biochemistry and Structural Biology, University of Texas Health San Antonio, San Antonio, TX.ORCID 0000-0001-9524-5323
Yanjun ChenDepartment of Biochemistry and Structural Biology, University of Texas Health San Antonio, San Antonio, TX.ORCID 0009-0000-2450-3401
Lorenzo CasalinoDepartment of Molecular Biology, University of California, San Diego, La Jolla, CA.ORCID 0000-0003-3581-1148
Hideki AiharaDepartment of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN.ORCID 0000-0001-7508-6230
Mark A HerzikDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA.ORCID 0000-0001-6653-6682
Reuben S HarrisDepartment of Biochemistry and Structural Biology, University of Texas Health San Antonio, San Antonio, TX.ORCID 0000-0002-9034-9112
Rommie E AmaroDepartment of Molecular Biology, University of California, San Diego, La Jolla, CA.ORCID 0000-0002-9275-9553

Funding

PROJECT 3 – BIOLOGY OF DNA DEAMINASES IN CANCERP01CA234228 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Reuben S Harris · 2019 to 2026
$14.5M
Contemporary Approaches to Cancer Cell Signaling and CommunicationT32CA009523 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DONOGHUE, DANIEL J, YANG, JING · 1985 to 2025
$12.1M
Structural studies of viral replication and invasionR35GM118047 · NIGMS · UNIVERSITY OF MINNESOTA · PI Hideki Aihara · 2016 to 2026
$6.3M
NCI NIH HHS T32 CA009523NIGMS NIH HHS R35 GM118047
6 · The paper itself

Abstract

APOBEC3B (A3B) is implicated in DNA mutations that facilitate tumor evolution. Although structures of its individual N- and C-terminal domains (NTD and CTD) have been resolved through X-ray crystallography, the full-length A3B (fl-A3B) structure remains elusive, limiting understanding of its dynamics and mechanisms. In particular, the APOBEC3B C-terminal domain (A3Bctd) active site is frequently closed in models and structures. In this study, we built several new models of fl-A3B using integrative structural biology methods and selected a top model for further dynamical investigation. We compared dynamics of the truncated (A3Bctd) to the fl-A3B via conventional and Gaussian accelerated molecular dynamics (MD) simulations. Subsequently, we employed weighted ensemble methods to explore the fl-A3B active site opening mechanism, finding that interactions at the NTD-CTD interface enhance the opening frequency of the fl-A3B active site. Our findings shed light on the structural dynamics of fl-A3B, which may offer new avenues for therapeutic intervention in cancer.

Indexed as

active site openingfull-length APOBEC3BGaussian accelerated molecular dynamics simulationsmolecular dynamics simulationsprotein dynamicsprotein-nucleic acid interactionsweighted ensemble method simulations

Identifiers

PMID39713448
PMCPMC11661193

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.