The objective of the study was to investigate structural changes in the protein-rich, high-molecular-weight fraction of coffee during roasting and their contribution to the melanoidin formation in the course of the Maillard reaction. For this purpose, high- and low-molecular-weight fractions of one raw and five coffee beans with an increased roasting degree were analyzed in terms of general (color, molecular weight, functionality, elemental composition) and specific parameters (amino acid composition, Maillard reaction products). It could be demonstrated that the high -molecular-weight fraction undergoes significant changes during roasting, where proteins appear to play an important role in melanoidin formation due to their diverse nucleophilic side chains. Modification of the amino acid side chains with known Maillard reaction products (MRPs) occurs in the early stages of roasting and decreases rapidly as color development progresses. The decrease suggests that MRPs are involved in further reactions and thus extend the functionality of the amino acid side chains, opening further possibilities for protein modification. Overall, the large number of reaction pathways leads to the formation of a well-mixed, continuous melanoidin spectrum covering a wide range of molecular masses. In this process, cross-linking and fragmentation reactions oppose each other, leading to an approximation of the molecular weight.