Year: 2020
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,380
Awards: G2368486158, Molecular Mechanisms in Adhesion Protein Mediated Neuron-Neuron Recognition, Computer Studies of Protein Structure and Function, G5553527218, COMPUTER STUDIES OF PROTEIN STRUCTURE AND FUNCTION, The structural basis of cis and trans protocadherin interactions, The Molecular Basis of Cadherin-Mediated Cell Adhesion, G9000067001
OpenAlex ID: W3022888162