Protein binding specificity versus promiscuity
Interactions between macromolecules in general, and between proteins in particular, are essential for any life process. Examples include transfer of information, inhibition or activation of function, molecular recognition as in the immune system, assembly of macromolecular structures and molecular m...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2015
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| Online Access: | http://hdl.handle.net/1721.1/99132 https://orcid.org/0000-0003-4074-8980 |
| _version_ | 1826215992531877888 |
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| author | Schreiber, Gideon Keating, Amy E. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Schreiber, Gideon Keating, Amy E. |
| author_sort | Schreiber, Gideon |
| collection | MIT |
| description | Interactions between macromolecules in general, and between proteins in particular, are essential for any life process. Examples include transfer of information, inhibition or activation of function, molecular recognition as in the immune system, assembly of macromolecular structures and molecular machines, and more. Proteins interact with affinities ranging from millimolar to femtomolar and, because affinity determines the concentration required to obtain 50% binding, the amount of different complexes formed is very much related to local concentrations. Although the concentration of a specific binding partner is usually quite low in the cell (nanomolar to micromolar), the total concentration of other macromolecules is very high, allowing weak and non-specific interactions to play important roles. In this review we address the question of binding specificity, that is, how do some proteins maintain monogamous relations while others are clearly polygamous. We examine recent work that addresses the molecular and structural basis for specificity versus promiscuity. We show through examples how multiple solutions exist to achieve binding via similar interfaces and how protein specificity can be tuned using both positive and negative selection (specificity by demand). Binding of a protein to numerous partners can be promoted through variation in which residues are used for binding, conformational plasticity and/or post-translational modification. Natively unstructured regions represent the extreme case in which structure is obtained only upon binding. Many natively unstructured proteins serve as hubs in protein–protein interaction networks and such promiscuity can be of functional importance in biology. |
| first_indexed | 2024-09-23T16:40:40Z |
| format | Article |
| id | mit-1721.1/99132 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:40:40Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/991322022-09-29T20:41:46Z Protein binding specificity versus promiscuity Schreiber, Gideon Keating, Amy E. Massachusetts Institute of Technology. Department of Biology Keating, Amy E. Interactions between macromolecules in general, and between proteins in particular, are essential for any life process. Examples include transfer of information, inhibition or activation of function, molecular recognition as in the immune system, assembly of macromolecular structures and molecular machines, and more. Proteins interact with affinities ranging from millimolar to femtomolar and, because affinity determines the concentration required to obtain 50% binding, the amount of different complexes formed is very much related to local concentrations. Although the concentration of a specific binding partner is usually quite low in the cell (nanomolar to micromolar), the total concentration of other macromolecules is very high, allowing weak and non-specific interactions to play important roles. In this review we address the question of binding specificity, that is, how do some proteins maintain monogamous relations while others are clearly polygamous. We examine recent work that addresses the molecular and structural basis for specificity versus promiscuity. We show through examples how multiple solutions exist to achieve binding via similar interfaces and how protein specificity can be tuned using both positive and negative selection (specificity by demand). Binding of a protein to numerous partners can be promoted through variation in which residues are used for binding, conformational plasticity and/or post-translational modification. Natively unstructured regions represent the extreme case in which structure is obtained only upon binding. Many natively unstructured proteins serve as hubs in protein–protein interaction networks and such promiscuity can be of functional importance in biology. National Institutes of Health (U.S.) (Award GM084181) National Institutes of Health (U.S.) (Award GM067681) 2015-10-02T17:11:25Z 2015-10-02T17:11:25Z 2010-11 Article http://purl.org/eprint/type/JournalArticle 0959440X http://hdl.handle.net/1721.1/99132 Schreiber, Gideon, and Amy E Keating. “Protein Binding Specificity Versus Promiscuity.” Current Opinion in Structural Biology 21, no. 1 (February 2011): 50–61. https://orcid.org/0000-0003-4074-8980 en_US http://dx.doi.org/10.1016/j.sbi.2010.10.002 Current Opinion in Structural Biology Creative Commons Attribution-Noncommercial-NoDerivatives http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Schreiber, Gideon Keating, Amy E. Protein binding specificity versus promiscuity |
| title | Protein binding specificity versus promiscuity |
| title_full | Protein binding specificity versus promiscuity |
| title_fullStr | Protein binding specificity versus promiscuity |
| title_full_unstemmed | Protein binding specificity versus promiscuity |
| title_short | Protein binding specificity versus promiscuity |
| title_sort | protein binding specificity versus promiscuity |
| url | http://hdl.handle.net/1721.1/99132 https://orcid.org/0000-0003-4074-8980 |
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