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Protein self-association is a widespread phenomenon that results in the formation of multimeric protein structures with critical roles in cellular processes. Protein self-association can lead to finite protein complexes or open-ended, and potentially, infinite structures. This review explores the concept of protein agglomeration, a process that results from the infinite self-assembly of folded proteins. We highlight its differences from other better-described processes with similar macroscopic features, such as aggregation and liquid-liquid phase separation. We review the sequence, structural, and biophysical factors influencing protein agglomeration. Lastly, we briefly discuss the implications of agglomeration in evolution, disease, and aging. Overall, this review highlights the need to study protein agglomeration for a better understanding of cellular processes., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2023.)

CD2 associated protein (CD2AP) is an adaptor protein that plays an important role in cell to cell union needed for the kidney function. CD2AP interacts, as an adaptor protein, with different natural targets, such as CD2, nefrin, c-Cbl and podocin. These proteins are believed to interact to one of the three SH3 domains that are positioned in the N-terminal region of CD2AP. To understand the network of interactions between the natural targets and the three SH3 domains (SH3-A, B and C), we have started to determine the structures of the individual SH3 domains. Here we present the high-resolution structure of the SH3-C domain derived from NMR data. Full backbone and side-chain assignments were obtained from triple-resonance spectra. The structure was determined from distance restraints derived from high-resolution 600 and 800 MHz NOESY spectra, together with phi and psi torsion angle restraints based on the analysis of 1HN, 15N, 1Halpha, 13Calpha, 13CO and 13Cbeta chemical shifts. Structures were calculated using CYANA and refined in water using RECOORD. The three-dimensional structure of CD2AP SH3-C contains all the features that are typically found in other SH3 domains, including the general binding site for the recognition of polyproline sequences.