HEИндивидуална стипендия2022–2024

GPIDR · Understanding the genetic encoding of dynamic interactions underlying transcriptional regulation

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2022-07-15 → 2024-07-14
Финансиране от ЕС: 165 313 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Взаимодействията между протеини без стабилна структура се изучават чрез модела на домейна PDZ3 и пептида CRIPT. Разбирането на тези процеси помага при изясняването на фундаменталната биология, човешките заболявания и откриването на нови лекарства.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Understanding the genetic encoding of dynamic interactions underlying transcriptional regulation

Protein-protein interactions underlie a wealth of important biological functions. While many of these interactions occur between proteins or parts of proteins that have stable structures, a large portion of them occur in proteins that are interacting in a more dynamic way, often facilitated by so-called "intrinsic disorder". Indeed, one third of the eukaryotic proteome is made up of these intrinsically disordered regions that do not have a stable structure, many of which remain uncharacterized. Understanding how intrinsically disordered proteins engage in dynamic protein-protein interactions not only has important implications for fundamental biology, but also for understanding human disease and enabling drug discovery. In order to address this gap in knowledge, we focused our study on an interaction between a model protein domain (PDZ3) and a disordered peptide (CRIPT). When the domain and peptide interact, one half of the peptide becomes stable, while the other half remains dynamic, or "fuzzy". This feature of the system enabled us to study both modes of interaction in the same system, providing us with directly comparable results that we could use to understand how two aspects of protein binding, affinity (how strongly the protein binds) and specificity (how selectively the protein binds), are encoded for fuzzy and non-fuzzy binding modes.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Transcription factors often serve as key hubs for dynamic protein-protein interactions in eukaryotic cells. Aside from their characteristic DNA binding domains, the vast majority of transcription factors contain activation domains that are often intrinsically disordered. These domains are not well-characterized, but are thought to contain key sequence-distributed features that enable transcription factors to interact with their many binding partners, and have recently been associated with the capacity to form transcriptional condensates through phase separation. Many questions remain about how genotype and phenotype are related in these relatively uncharacterized regions, particularly with respect to their dynamic binding interactions, with important implications for human disease-associated mutations. Here, we propose to help uncover the relationships between sequence, structure, and dynamics of these interactions in vivo, using the power of deep mutational scanning and protein complementation assays in budding yeast.

Оригинален текст от CORDIS (на английски).

Участници

FUNDACIO CENTRE DE REGULACIO GENOMICA · BarcelonaКоординаторИспания