DIP/Dpr interactions and the evolutionary design of specificity in protein families

Alina P. Sergeeva, Phinikoula S. Katsamba, Filip Cosmanescu, Joshua J. Brewer, Goran Ahlsen, Seetha Mannepalli, Lawrence Shapiro () and Barry Honig ()
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Alina P. Sergeeva: Columbia University
Phinikoula S. Katsamba: Columbia University
Filip Cosmanescu: Columbia University
Joshua J. Brewer: Columbia University
Goran Ahlsen: Columbia University
Seetha Mannepalli: Columbia University
Lawrence Shapiro: Columbia University
Barry Honig: Columbia University

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Differential binding affinities among closely related protein family members underlie many biological phenomena, including cell-cell recognition. Drosophila DIP and Dpr proteins mediate neuronal targeting in the fly through highly specific protein-protein interactions. We show here that DIPs/Dprs segregate into seven specificity subgroups defined by binding preferences between their DIP and Dpr members. We then describe a sequence-, structure- and energy-based computational approach, combined with experimental binding affinity measurements, to reveal how specificity is coded on the canonical DIP/Dpr interface. We show that binding specificity of DIP/Dpr subgroups is controlled by “negative constraints”, which interfere with binding. To achieve specificity, each subgroup utilizes a different combination of negative constraints, which are broadly distributed and cover the majority of the protein-protein interface. We discuss the structural origins of negative constraints, and potential general implications for the evolutionary origins of binding specificity in multi-protein families.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15981-8

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DOI: 10.1038/s41467-020-15981-8

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