Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages.

Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages. Research Abstract Details 

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Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages. Abstract Text:

Antonio Del Sol,Marcos J ,Dolors Amoros,Ruth Nussinov,

BACKGROUND: Allosteric communications are vital for cellular signaling. Here we explore a relationship between protein architectural organization and shortcuts in signaling pathways. RESULTS: We show that protein domains consist of modules interconnected by residues that mediate signaling through the shortest pathways. These mediating residues tend to be located at the inter-modular boundaries, which are more rigid and display a larger number of long-range interactions than intra-modular regions. The inter-modular boundaries contain most of the residues centrally conserved in the protein fold, which may be crucial for information transfer between amino acids. Our approach to modular decomposition relies on a representation of protein structures as residue-interacting networks, and removal of the most central residue contacts, which are assumed to be crucial for allosteric communications. The modular decomposition of 100 multi-domain protein structures indicates that modules constitute the building blocks of domains. The analysis of 13 allosteric proteins revealed that modules characterize experimentally identified functional regions. Based on the study of an additional functionally annotated dataset of 115 proteins, we propose that high-modularity modules include functional sites and are the basic functional units. We provide examples (the Galphas subunit and P450 cytochromes) to illustrate that the modular architecture of active sites is linked to their functional specialization. CONCLUSION: Our method decomposes protein structures into modules, allowing the study of signal transmission between functional sites. A modular configuration might be advantageous: it allows signaling proteins to expand their regulatory linkages and may elicit a broader range of control mechanisms either via modular combinations or through modulation of inter-modular linkages.

Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages. Publishing Authors By Initials

A Del Sol,MJ ,D Amoros,R Nussinov,

For similar biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research abstracts see: biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research

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Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Intr

Journal: Genome biology

VOLUME: 8

Page Numbers: R92

Journal Abbreviation: Genome Biol.

ISSN: 1465-6914

DAY: 3

MONTH: 12

YEAR: 2007

Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100960660

Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages. Keywords Mesh Terms:

KEYWORDS: Signal Transduction

MESH TERMS: chemistry

Chemical & Substance for Abstract: Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages. Information

Substance Name: Proteins

Registry Number: 0

Grant and Affiliation Information for Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages.

AFFILIATION: Bioinformatics Research Unit, Research and Development Division, Fujirebio Inc, Komiya-cho, Hachioji-shi, Tokyo 192-0031, Japan. ao-mesa@fujirebio.co.jp

Country: England

AGENCY: United States NCI

GRANT: N01-CO-12400

ACRONYM: CO

MEDLINETA: Genome Biol

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