Evidence map›Paper›PMID 25756188›Full record

ArticleBiochemistry2015

Adaptive mutations alter antibody structure and dynamics during affinity maturation.

Ramkrishna Adhikary, Wayne Yu, Masayuki Oda, Ross C Walker, Tingjian Chen, Robyn L Stanfield, Ian A Wilson, Jörg Zimmermann, Floyd E Romesberg

Abstract read
In one paragraph

Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing 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

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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

20 citing papers in PubMed.

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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

9 authors.

Ramkrishna Adhikary
Wayne Yu
Masayuki Oda§Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5, Hangi-cho, Shimogamo, Sakyo-ku, Kyoto 606-8522, Japan.
Ross C Walker∥Department of Chemistry and Biochemistry and San Diego Supercomputer Center, University of California, San Diego, La Jolla, California 92093, United States.
Tingjian Chen
Robyn L Stanfield
Ian A Wilson
Jörg Zimmermann
Floyd E Romesberg

Funding

EXPANDING THE GENETIC ALPHABET BY POLYMERASE EVOLUTIONR01GM060005 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI ROMESBERG, FLOYD E. · 1999 to 2015
$4.6M
The Contribution of Protein Dynamics to Antibody Affinity MaturationR56AI079319 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI ROMESBERG, FLOYD E. · 2009 to 2009
$433k
NCI NIH HHS Y01 CO001020NCI NIH HHS Y1-CO-1020NIAID NIH HHS AI079319NIAID NIH HHS R56 AI079319NIGMS NIH HHS R01 GM060005NIGMS NIH HHS Y01 GM001104NIGMS NIH HHS Y1-GM-1104
6 · The paper itself

Abstract

While adaptive mutations can bestow new functions on proteins via the introduction or optimization of reactive centers, or other structural changes, a role for the optimization of protein dynamics also seems likely but has been more difficult to evaluate. Antibody (Ab) affinity maturation is an example of adaptive evolution wherein the adaptive mutations may be identified and Abs may be raised to specific targets that facilitate the characterization of protein dynamics. Here, we report the characterization of three affinity matured Abs that evolved from a common germline precursor to bind the chromophoric antigen (Ag), 8-methoxypyrene-1,3,6-trisulfonate (MPTS). In addition to characterizing the sequence, molecular recognition, and structure of each Ab, we characterized the dynamics of each complex by determining their mechanical response to an applied force via three-pulse photon echo peak shift (3PEPS) spectroscopy and deconvoluting the response into elastic, anelastic, and plastic components. We find that for one Ab, affinity maturation was accomplished via the introduction of a single functional group that mediates a direct contact with MPTS and results in a complex with little anelasticity or plasticity. In the other two cases, more mutations were introduced but none directly contact MPTS, and while their effects on structure are subtle, their effects on anelasticity and plasticity are significant, with the level of plasticity correlated with specificity, suggesting that the optimization of protein dynamics may have contributed to affinity maturation. A similar optimization of structure and dynamics may contribute to the evolution of other proteins.

Indexed as

Antibody SpecificityEvolution, MolecularModels, ImmunologicalModels, MolecularMutationAmino Acid SubstitutionAnimalsAntibodies, MonoclonalAntibody AffinityBinding Sites, AntibodyFluorescent DyesHybridomasHydrogen BondingImmunoglobulin GKineticsMice8-methoxypyrene-1,3,6-trisulfonic acid trisodium saltAntibodies, MonoclonalFluorescent DyesImmunoglobulin GPyrenes

Identifiers

PMID25756188
PMCPMC5061043

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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.